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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002212-13 | EudraCT Number |
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The study was terminated due to pre-specified futility criteria met.
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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The study consisted of 2 parts: Dose Escalation phase (Part A) and Expansion phase (Part B). The dose escalation phase evaluated the safety, tolerability, and PK of avelumab in combination with M9241 in subjects with locally advanced, unresectable, or metastatic solid tumors. Expansion phase assessed the safety and clinical activity of the combination regimen in selected tumor types. In Expansion phase subjects who had completed the combination treatment of avelumab at a given dose level of M9241, a safety review was performed by the Safety monitoring committee in order to make a decision on the next dose level. Successive cohorts of 3 to 6 subjects were treated with escalating doses of M9241 with avelumab intravenous (IV).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Experimental | Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Experimental | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Experimental | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avelumab | Drug | Participants received avelumab intravenous (IV) infusion once a week on Day 1 and Day 15 of each cycle. |
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| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported. | From first dose of study treatment up to 1311 days |
| Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported. | Part B: From first dose of study treatment up to 443 days |
| Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. | Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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Inclusion Criteria:
Part A:
subjects must had signed written informed consent.
male or female subjects age greater than equals to (>=)18 years.
subjects must had histologically or cytologically proven metastatic or locally advanced solid tumors for which no standard therapy exists, standard therapy had failed, subject was intolerant of established therapy known to provided clinical benefit for their condition, or standard therapy was not acceptable to subject.
subjects who had been treated previously with a checkpoint inhibitor may enroll (except as outlined below for expansion cohorts).
at least 1 unidimensional radiographically measurable lesion based on response evaluation criteria in solid tumors (recist) version 1. 1 (v1. 1), except for subjects with metastatic castration-resistant prostate cancer (crpc) or metastatic breast cancer who may been enrolled with objective evidence of disease without a measureable lesion. - eastern cooperative oncology group (ecog) performance status of 0 to 1 at screening
estimated life expectancy of more than 12 weeks
adequate hematological function as defined below:
adequate hepatic function as defined below:
adequate renal function as defined by an estimated creatinine clearance >= 50 milliliter per minute (ml/min) according to cockcroft-gault formula
negative blood pregnancy test at screening for women of childbearing potential. For purposes of this trial, women of childbearing potential were defined as all female subjects after puberty unless they were postmenopausal for at least 1 year, surgically sterile or sexually inactive.
highly effective contraception (ie, methods with a failure rate of less than 1% per year) must been used before started of treatment, for duration of trial treatment, and for at least 50 days after stopping studied treatment for both men and women if risk of conception exists. The effects of avelumab and m9241 on developing human fetus were unknown; thus, women of childbearing potential and men agreed to use highly effective contraception.
Part B:
Exclusion Criteria:
Concurrent treatment with a non-permitted drug/intervention (listed below)
Any prior treatment with any form of interlukin-12 (IL-12)
For the NSCLC, CRC, and UC expansion cohorts, prior therapy with any antibody / drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) antibody was prohibited.
Intolerance to checkpoint inhibitor therapy, as defined by the occurrence of an AE requiring drug discontinuation. - Active or history of primary or metastatic central nervous system tumors
Prior organ transplantation, including allogeneic stem-cell transplantation
Previous malignant disease (other than the indication for this trial) within the last 5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to trial entry and subject was deemed to have been cured with no additional therapy required or anticipated to be required.
Significant acute or chronic infections requiring systemic therapy including, among others:
• History of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome • Hepatitis B or C infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV deoxy ribonucleic acid (DNA) or HBV core antibody positive alone with reflex to positive HBV DNA or positive hepatitis C virus [HCV] antibody with reflex to positive HCV ribonucleic acid [RNA]). Participants with history of infection must had polymerase chain reaction documentation that infection was cleared.
Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment wer eligible if they wer stable on other medical treatment and do not fulfill exclusion criterion including Uncontrolled intercurrent illness - Known severe hypersensitivity reactions to monoclonal antibodies (Grade>= 3 National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma)
History of allergic reaction to methotrexate (trace methotrexate may be present in M9241 as a part of manufacturing process) or history of severe hypersensitivity reaction to any other ingredient of study drug(s) and / or their excipients. Since M9241 contains sucrose as an excipient, participants suffering from hereditary fructose intolerance also excluded - Persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v4.03 with the following exceptions:
Pregnancy or lactation
Known alcohol or drug abuse as deemed by the Investigator
Uncontrolled intercurrent illness including, but not limited to:
Clinically significant (or active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class >= II), or serious cardiac arrhythmia requiring medication
All other significant diseases (eg, inflammatory bowel disease, current severe acute or chronic colitis) or chronic medical conditions (including laboratory abnormalities) that in opinion of Investigator might impair subject's tolerance of trial treatment or interpretation of trial results.
Any psychiatric condition that would prohibit understanding or endering of informed consent or that would limit compliance with trial requirements.
Legal incapacity or limited legal capacity.
Administration of a live vaccine within 30 days prior to trial entry.
Any subject with possible area of ongoing necrosis (non-disease related), such as active ulcer, non-healing wound, or intercurrent bone fracture that may be at risk of delayed healing due to protocol therapy.
Oxygen saturation < 90% at rest, known pulmonary fibrosis, or active interstitial lung disease.
History of congenital or active immunodeficiency, with exception of acquired treatment-related hypogammaglobulinemia requiring periodic IV immunoglobulin infusion.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Cancer Associates for Research & Excellence, Inc. | San Diego | California | 92111 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37236636 | Result | Strauss J, Deville JL, Sznol M, Ravaud A, Maruzzo M, Pachynski RK, Gourdin TS, Maio M, Dirix L, Schlom J, Donahue RN, Tsai YT, Wang X, Vugmeyster Y, Beier F, Seebeck J, Schroeder A, Chennoufi S, Gulley JL. First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma. J Immunother Cancer. 2023 May;11(5):e005813. doi: 10.1136/jitc-2022-005813. |
| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
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We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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The study was conducted at 33 sites within Europe and the United States.
The study consisted of 2 parts: Part A (Dose escalation) and Part B (Dose expansion).
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 22, 2019 | May 13, 2024 |
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Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Experimental | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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| Part B Cohort 1: UC Cohort Stage 1 combination therapy | Experimental | Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study. |
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| M9241 | Drug | Participants received Subcutaneous (SC) injection of M9241 in escalating doses on Day 1 of each cycle. |
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| Avelumab (Once weekly) | Drug | Participants received avelumab once weekly in combination with M9241 every 4 weeks at M9241 maximum tolerated dose (MTD) for first 12 weeks followed by avelumab once every 2 weeks plus M9241 once every 4 weeks at M9241 MTD until a criterion for treatment discontinuation has been met. |
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| M9241 (MTD) | Drug | Participants received M9241 at M9241 MTD once every 4 weeks until a criterion for treatment discontinuation has been met. |
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| Avelumab (Expansion cohort) | Drug | Participants in the expansion cohorts received Induction Therapy (Avelumab once weekly + M9241 once every 4 weeks) through Cycle 3 (for 12 weeks) then starting at Cycle 4, Continuation Therapy (Avelumab once every 2 weeks + M9241 once every 4 weeks). |
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AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported. |
| From first dose of study treatment up to 1311 days |
| Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported. | First dose of study drug up to 443 days |
| Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | A DLT is any Grade (>=) 3 non-hematologic AE or any Grade (>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade >=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to <= Grade 2 within 7 days of initiating therapy will be a DLT. Any Grade 4 neutropenia of < 5 days duration; Grade 3 infusion-related reaction resolving within 6 hours of infusion; Grade 3 diarrhea or skin toxicity that resolves to Grade <= 1 within 7 days after medical management; Transient Grade 3 fatigue, local reactions, flu-like symptoms; Tumor flare phenomenon of known or suspected tumor did not consider a DLT. | Time from first treatment to final assessment up to 3 weeks |
| Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Not evaluable (NE): No post-baseline assessment. BOR assessments were assessed by investigators. | First dose of study drug up to 443 days |
| Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method. | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve. | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
| Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). (AUC0-t) was calculated according to the mixed log-linear trapezoidal rule. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Apparent Terminal Half-life (t1/2) of M9241 | Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
| Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at >=8-fold baseline titer), or treatment-emergent (TE [any positive post baseline assay response when baseline results were negative or missing or not reported]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period [based on nominal sampling time], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples). | First dose of study drug up to 1311 days |
| Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | BOR is defined as best response of any of confirmed complete response, confirmed partial response, stable disease and progressive disease recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Non-CR/non-PD (for participants with non-measurable disease at baseline) = at least one Non-CR/non-PD assessment (or better) >= 6 weeks after first study treatment administration and before progression and Not Evaluable: all other cases. BOR assessments were assessed by investigators. | First dose of study drug up to 1311 days |
| Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | BOR: best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported. | First dose of study drug up to 1311 days |
| Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | PFS was defined as the time from first treatment day until date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier estimates. | Time from first dose administration until progressive disease or death, assessed up to 443 days |
| Part B: Overall Survival (OS) Time | The OS time was defined as the time from treatment day 1 to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier estimates. | Time from first dose of study treatment up to 443 days |
| Part B: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | DOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. If a participant has not an event (PD or death), DOR was censored at the date of last adequate tumor assessment. | Time from first dose of study treatment up to 443 days |
| Part B: Maximum Observed Serum Concentration (Cmax) of M9241 | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. | Pre-dose, 1 hour post-dose on Day 1 and Day 29 of Cycle 1 and 2 (Each cycle: 28 days) |
| Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Ctrough was defined as the trough or minimum serum concentration. | Pre-dose, 1 hour post-dose on Day 1 of cycle 2; Day 1, 27 of cycle 3; Day 1 of cycle 5 (Each cycle: 28 days) |
| Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Ceoi is the observed serum drug concentration at the end of Intravenous (IV) infusion. | Pre-dose, 1 hour post-dose on Day 1 and 15 of Cycle 1 and 2 (Each cycle: 28 days) |
| Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab | Ctrough was defined as the trough or minimum serum concentration. | Pre-dose, 1 hour post-dose on Day 15, 29 and 43 |
| Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at >=8-fold baseline titer), or treatment-emergent (TE [any positive post baseline assay response when baseline results were negative or missing or not reported]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period [based on nominal sampling time], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples). | Time from first dose of study treatment up to 443 days |
| Sharp Memorial Hospital |
| San Diego |
| California |
| 92123 |
| United States |
| St Joseph Heritage Healthcare | Santa Rosa | California | 95403 | United States |
| Yale University Institutional Review Board | New Haven | Connecticut | 06520 | United States |
| Holy Cross Hospital Inc. | Fort Lauderdale | Florida | 33308 | United States |
| Hematology - Oncology Associates of the Treasure Coast | Port Saint Lucie | Florida | 34952 | United States |
| Metairie Oncologists, LLC | Metairie | Louisiana | 70006 | United States |
| National Cancer Institute | Bethesda | Maryland | 20892 | United States |
| Virginia Piper Cancer Institute | Minneapolis | Minnesota | 55407 | United States |
| Washington University | St Louis | Missouri | 63110 | United States |
| UC Health, LLC. | Cincinnati | Ohio | 45229 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Cedar Sinai Medical Center | Ashland | Oregon | 97520 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Mary Crowley Cancer Research Centers | Dallas | Texas | 75251 | United States |
| University of Vermont Medical Center | Burlington | Vermont | 05405 | United States |
| Northwest Medical Specialties, PLLC | Tacoma | Washington | 98405 | United States |
| Centre Hospitalier de l'Ardenne - Pharmacie | Libramont | Belgium |
| GZA Ziekenhuizen - Campus Sint-Augustinus | Wilrijk | Belgium |
| CHU Bordeaux - Hôpital Saint André | Bordeaux | France |
| Centre Georges François Leclerc | Dijon | France |
| Centre Oscar Lambret | Lille | France |
| Hôpital de la Timone# - CPCEM CIC - Bat F 1er étage | Marseille | France |
| Centre Hospitalier Lyon Sud | Pierre-Bénite | France |
| Centre Paul Strauss | Strasbourg | France |
| Orszagos Onkologiai Intezet | Budapest | Hungary |
| Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | Italy |
| IOV - Istituto Oncologico Veneto IRCCS | Padova | Italy |
| A.O.U. Senese Policlinico Santa Maria alle Scotte | Siena | Italy |
| Amsterdam UMC, Locatie VUMC | Amsterdam | Netherlands |
| Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | Netherlands |
| Maastricht University Medical Center | Maastricht | Netherlands |
| Hospital Universitario Virgen del Rocio | Seville | Spain |
| US Medical Information website, Medical Resources | View source |
| FG001 | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| FG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| FG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| FG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental) | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| FG005 | Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental) | Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study. |
| COMPLETED |
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| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| BG001 | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| BG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| BG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| BG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental) | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| BG005 | Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental) | Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
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| Primary | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported. | Safety analysis set (SAF) included all participants who receive at least 1 dose (complete or incomplete) of any investigational medicinal product (IMP) (Avelumab or NHS-IL12). | Posted | Count of Participants | Participants | From first dose of study treatment up to 1311 days |
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| Primary | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported. | SAF included all participants who receive at least 1 dose of any investigational medicinal product (IMP) (Avelumab or NHS-IL12). | Posted | Count of Participants | Participants | Part B: From first dose of study treatment up to 443 days |
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| Primary | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported. | SAF analysis set included all participants who receive at least 1 dose (complete or incomplete) of any IMP (Avelumab or NHS-IL12). | Posted | Count of Participants | Participants | From first dose of study treatment up to 1311 days |
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| Primary | Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported. | SAF analysis set included all participants who receive at least 1 dose (complete or incomplete) of any IMP (Avelumab or NHS-IL12). Here, "overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Count of Participants | Participants | No | First dose of study drug up to 443 days |
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| Primary | Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | A DLT is any Grade (>=) 3 non-hematologic AE or any Grade (>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade >=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to <= Grade 2 within 7 days of initiating therapy will be a DLT. Any Grade 4 neutropenia of < 5 days duration; Grade 3 infusion-related reaction resolving within 6 hours of infusion; Grade 3 diarrhea or skin toxicity that resolves to Grade <= 1 within 7 days after medical management; Transient Grade 3 fatigue, local reactions, flu-like symptoms; Tumor flare phenomenon of known or suspected tumor did not consider a DLT. | DLTs analysis set included all participants who received all treatment in the DLT period or stopped treatment because of DLTs in the DLT period. | Posted | Count of Participants | Participants | Time from first treatment to final assessment up to 3 weeks |
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| Primary | Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Not evaluable (NE): No post-baseline assessment. BOR assessments were assessed by investigators. | Full analysis set included all participants who received at least 1 dose of any study treatment. | Posted | Count of Participants | Participants | First dose of study drug up to 443 days |
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| Secondary | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour per milliliter (mcg*h/mL) | Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour per milliliter (mcg*h/mL) | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | One per hour (1/hour) | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram/milliliter (mcg/mL) | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Median | Full Range | hours | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Median | Full Range | hours | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg*h/mL | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) |
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| Secondary | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). (AUC0-t) was calculated according to the mixed log-linear trapezoidal rule. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter (ng*h/mL) | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. | Pharmacokinetic analysis set included participants who completed at least 1 administration of avelumab and/or M9241 and provided at least 1 sample with a measurable concentration. Here, "Overall Number of participants analyzed", signifies participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable at the specified time point. None of the participants were analyzed in Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg arm at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method. | Pharmacokinetic analysis set included participants who completed at least 1 administration of avelumab and/or M9241 and provided at least 1 sample with a measurable concentration. Here, "Overall Number of participants analyzed", signifies participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable at the specified time point. None of the participants were analyzed in Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg arm at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | One per hour (1/hour) | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Mean | Standard Deviation | ng/mL | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Median | Full Range | hours | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Median | Full Range | hours | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Pharmacokinetic analysis set included participants who completed at least 1 administration of avelumab and/or M9241 and provided at least 1 sample with a measurable concentration. Here, "Overall Number of participants analyzed", signifies participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable at the specified time point. None of the participants were analyzed in Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg arm at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) |
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| Secondary | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at >=8-fold baseline titer), or treatment-emergent (TE [any positive post baseline assay response when baseline results were negative or missing or not reported]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period [based on nominal sampling time], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples). | Immunogenicity analysis set included all participants who received at least 1 complete dose (at least 90% of planned dose) of any study treatment & at least 1 valid ADA result for avelumab or NHS-IL12. | Posted | Count of Participants | Participants | First dose of study drug up to 1311 days |
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| Secondary | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | BOR is defined as best response of any of confirmed complete response, confirmed partial response, stable disease and progressive disease recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Non-CR/non-PD (for participants with non-measurable disease at baseline) = at least one Non-CR/non-PD assessment (or better) >= 6 weeks after first study treatment administration and before progression and Not Evaluable: all other cases. BOR assessments were assessed by investigators. | Full analysis set included all participants who received at least 1 dose of any study treatment. | Posted | Count of Participants | Participants | First dose of study drug up to 1311 days |
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| Secondary | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | BOR: best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported. | Full analysis set included all participants who received at least 1 dose of any study treatment. | Posted | Count of Participants | Participants | First dose of study drug up to 1311 days |
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| Secondary | Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | PFS was defined as the time from first treatment day until date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier estimates. | Full analysis set included all participants who received at least 1 dose of any study treatment. | Posted | Median | 95% Confidence Interval | weeks | Time from first dose administration until progressive disease or death, assessed up to 443 days |
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| Secondary | Part B: Overall Survival (OS) Time | The OS time was defined as the time from treatment day 1 to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier estimates. | Full analysis set included all participants who received at least 1 dose of any study treatment. | Posted | Median | 95% Confidence Interval | months | Time from first dose of study treatment up to 443 days |
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| Secondary | Part B: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | DOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. If a participant has not an event (PD or death), DOR was censored at the date of last adequate tumor assessment. | Data could not be calculated as none of the participants showed objective response. | Posted | Time from first dose of study treatment up to 443 days |
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| Secondary | Part B: Maximum Observed Serum Concentration (Cmax) of M9241 | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose, 1 hour post-dose on Day 1 and Day 29 of Cycle 1 and 2 (Each cycle: 28 days) |
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| Secondary | Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Ctrough was defined as the trough or minimum serum concentration. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose, 1 hour post-dose on Day 1 of cycle 2; Day 1, 27 of cycle 3; Day 1 of cycle 5 (Each cycle: 28 days) |
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| Secondary | Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Ceoi is the observed serum drug concentration at the end of Intravenous (IV) infusion. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, 1 hour post-dose on Day 1 and 15 of Cycle 1 and 2 (Each cycle: 28 days) |
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| Secondary | Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab | Ctrough was defined as the trough or minimum serum concentration. | Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, "Overall Number of participants analyzed", signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, 1 hour post-dose on Day 15, 29 and 43 |
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| Secondary | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at >=8-fold baseline titer), or treatment-emergent (TE [any positive post baseline assay response when baseline results were negative or missing or not reported]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period [based on nominal sampling time], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples). | Immunogenicity analysis set included all participants who received at least 1 complete dose (at least 90% of planned dose) of any study treatment & at least 1 valid ADA result for avelumab or NHS-IL12. | Posted | Count of Participants | Participants | Time from first dose of study treatment up to 443 days |
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Part A: Baseline up to 1311 days Part B: Baseline up to 443 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental) | Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 9 | 9 | 4 | 9 | 9 | 9 |
| EG001 | Part A Cohort 2: M9241 8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 5 | 7 | 4 | 7 | 7 | 7 |
| EG002 | Part A Cohort 3: M9241 12 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 6 | 7 | 3 | 7 | 7 | 7 |
| EG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 5 | 6 | 3 | 6 | 6 | 6 |
| EG004 | Part A Cohort 5: M9241 16.8 mcg/kg +Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 7 | 7 | 4 | 7 | 7 | 7 |
| EG005 | Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental) | Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study. | 12 | 16 | 12 | 16 | 16 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Autoimmune haemolytic anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Blood loss anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Retroperitoneal haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Gallbladder obstruction | Hepatobiliary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cystitis noninfective | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Renal haemorrhage | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Diverticular perforation | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary tract infection enterococcal | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary tract infection pseudomonal | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA 23.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Bundle branch block left | Cardiac disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Anal incontinence | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Gastroduodenal ulcer | Gastrointestinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Bacteriuria | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Vascular device infection | Infections and infestations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Injection site rash | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Injection site oedema | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Bilirubin conjugated increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Brain natriuretic peptide increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Clostridium test positive | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Red blood cell count decreased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypochloraemia | Metabolism and nutrition disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Soft tissue necrosis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Anosmia | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Resting tremor | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Oedema genital | Reproductive system and breast disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Penile pain | Reproductive system and breast disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pleural thickening | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Hydroureter | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Urinary fistula | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 23.1 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 23.1 | Non-systematic Assessment |
|
The study was terminated due to pre-specified futility criteria met.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck KGaA, Darmstadt, Germany | 6151 72 5200 | service@merckgroup.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 20, 2020 | May 13, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000609138 | avelumab |
| D020714 | Maximum Tolerated Dose |
| ID | Term |
|---|---|
| D018675 | Toxicity Tests |
| D008919 | Investigative Techniques |
| D000069436 | Toxicological Phenomena |
| D002620 | Pharmacological and Toxicological Phenomena |
| D010829 | Physiological Phenomena |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.
| Participants with Treatment-related-TEAEs |
|
|
|
Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
|
|
| OG001 | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
|
|
Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met.
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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| OG001 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg |
Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
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Participants received SC injection of M9241 at a dose of 8 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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|
Participants received SC injection of M9241 at a dose of 8 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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Participants received SC injection of M9241 at a dose of 8 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG001 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg |
Participants received SC injection of M9241 at a dose of 8 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG001 | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 8 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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| OG001 | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 8 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG002 | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Participants received SC injection of M9241 at a dose of 12 mcg/kg once every 4 week on Day 1 in combination with IV infusion of Avelumab 10 mg/kg once every 2 weeks on Day 1 and 15 of each cycle (each cycle is of 28 days) until any criterion for treatment discontinuation were met |
| OG003 | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. |
| OG004 | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Participants received IV infusion of avelumab at dose of 800 mg once weekly for the first 12 weeks in combination with SC injection of M9241, 16.8 mcg/kg once every 4 weeks, then avelumab at 800 mg IV infusion once every 2 weeks in combination with M9241 at dose of 16.8 mcg/kg SC injection once every 4 weeks until criteria for treatment discontinuation were met |
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