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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001002-26 | EudraCT Number |
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In the Phase II part of the study, among the participants evaluable for efficacy, no objective (partial response or clinical response) was observed at the first futility analysis.
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This is a Phase I/II, open-label, non-randomized, multicenter study to explore safety, tolerability and antitumor activity of NMS-01940153E as single agent in adult patients with unresectable hepatocellular carcinoma (HCC) previously treated with systemic therapy.
The Phase I portion is designed as a dose-escalation study in sequential cohorts of patients aimed to obtain the maximum tolerated dose (MTD) that is defined based on the dose limiting toxicities (DLTs) observed in the first cycle of treatment.
The Phase II portion is designed as a two-stage study with an interim analysis for futility and stopping criteria for unacceptable toxicity to assess the antitumor activity of NMS-01940153E in adult patients with unresectable HCC previously treated with systemic therapy measured as objective response rate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NMS-01940153E | Experimental | Phase I: Patients will be allocated to sequential cohorts of progressively higher dose levels of NMS-01940153E based on the presence of Dose Limiting Toxicities (DLT). Phase II: Patients will be treated at the recommended Phase II dose (RP2D) defined in the Phase I portion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NMS-01940153E | Drug | Route of administration: intravenous (IV) solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase I Drug Related Dose Limiting Toxicities (DLTs) | All 12 Phase I treated patients were evaluable for DLT (Dose-Limiting Toxicity Evaluable Set) and included 6 patients treated at each of the two dose levels explored (i.e., 100 mg/m2/week and 135 mg/m2/week) who received at least 66% of the study drug in the first 28-day cycle of treatment and underwent a DLT assessment within the DLT window. Participants who experienced DLTs are presented. | Phase I: From screening to end of first 28-day cycle (17 months) |
| Phase II Objective Response Rate | The objective response rate (ORR) was calculated as the proportion of evaluable patients who achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) measured by investigator-assessed RECIST 1.1 (Phase II). | Phase II: From Phase II start to Study Completion (23 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-emergent Adverse Events by Maximum CTC Grade | The maximum Common Terminology Criteria (CTC) grade (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. |
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Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
Exclusion Criteria:
The presence of any of the following will exclude a subject from study enrollment:
Known fibrolamellar HCC or mixed hepato-cholangiocarcinoma.
Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
Subjects with QT interval using Fridericia standard (QTcF) ≥480 milliseconds or with risk factors for torsade de pointes (e.g., heart failure, uncontrolled hypokalemia, family history of long QT syndrome) or receiving treatment with concomitant medications known to prolong the QT/QTc interval that cannot be replaced with another treatment.
Ascites defined as CTCAE Grade ≥2. Subjects who have been on a stable medication regimen for at least 2 months to manage ascites are eligible if they show ascites Grade <2.
Subjects with clinically undetectable ascites who are Child A with detectable ascites at CT/MRI are eligible.
Uncontrolled high blood pressure (systolic blood pressure, SBP >150 mmHg and/or diastolic blood pressure, DBP >95 mmHg, despite optimal treatment, on at least 2 out of 3 determinations repeated at 30 minutes interval and done in case that the first one meets the criterion for exclusion).
Direct-Acting Antivirals (DAA) at the time of treatment start; previous hepatitis C virus (HCV) treatment with DAAs is allowed.
Clinical evidence of hepatic encephalopathy.
Known brain metastases or evidence of leptomeningeal disease.
Known history of allergic reactions to polysorbate 80.
Any of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis (except chronic/stable portal vein thrombosis).
Major surgery, other than diagnostic surgery, within 4 weeks before treatment start.
Any anticancer agent within 4 weeks or, in absence of toxicity, 5 half-lives (within 6 weeks for nitrosureas, mitomycin C and liposomal doxorubicin) before treatment start.
Radiation therapy within 4 weeks or radionuclide treatment (e.g., I-131 or Y-90) within 6 weeks before treatment start.
Untreated uncontrolled bacterial, viral, or fungal infections including acute HIV infection or acquired immunodeficiency syndrome (AIDS), untreated uncontrolled HBV, untreated uncontrolled HCV, untreated uncontrolled concomitant HBV and HCV; patients who are seropositive following HBV vaccine are eligible.
Subjects under treatment with therapeutic dose of anticoagulants (e.g., warfarin or warfarin-related agents, low-molecular weight heparin, or similar agent such as anti Xa and anti-thrombin agents) or antiplatelet agents (e.g. clopidogrel) or with coagulation disorders. Aspirin at dose up to 100 mg is permitted. Prophylaxis with anticoagulants is allowed to meet the international normalized ratio (INR) value range as cited in inclusion criterion 9.
Uncontrolled diabetes mellitus.
Pregnant or breast-feeding women.
Known second malignancy that is progressing or requiring active treatment. Exceptions include adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri.
Current enrollment or participation in another interventional clinical trial.
Clinically significant respiratory or metabolic diseases uncontrolled by medication.
Subjects with active alcohol and/or substances abuse.
Any known organ dysfunction, serious illness, acute or chronic medical or psychiatric condition, or laboratory abnormality which, in the Investigator's opinion, may increase the risk associated/interfere with study participation, or with the interpretation of the results.
Subjects who, within 7 days prior to the first NMS-01940153E intake, are receiving or received strong inducers of flavin-containing monooxygenase FMO1 and FMO3.
Subjects who are receiving sensitive CYP3A4 substrates, CYP3A4 and breast cancer resistance protein (BCRP) substrates with narrow therapeutic index (NTI).
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Irvine Health | Orange | California | 92868-3201 | United States | ||
| Siteman Cancer Center - Washington University Medical Campus |
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1 Participants: 100 mg/m2/Week | All participants in Phase I who received 100 mg/m2/week intravenous NMS-01940153E. |
| FG001 | Phase I Participants: 135 mg/m2/Week | All participants in Phase I who received 135 mg/m2/week intravenous NMS-01940153E. |
| 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 | Jan 9, 2023 | Feb 19, 2025 |
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| Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
| Treatment-emergent Adverse Events Related to NMS-01940153E | The number of treatment-emergent adverse events related to NMS-01940153E by maximum CTC grade experienced (graded using NCI CTCAE Version 5.0). Whether the the AE was related or not was assessed by the investigator. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening. Phase 2 started before Phase 1 completed. | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
| Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Number of treatment emergent abnormalities (at any grade) at all dose levels are presented. CTC = Common Terminology Criteria WBC = white blood cells | From screening to 28 days follow-up, an average 6 months |
| Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | The mean days to first occurrence of neutrophil count decrease are presented for all dose levels. Grade 0: ≥2,000/mm3 Grade 1: ≥1,500-< 2,000/mm3 Grade 2: ≥1,000- < 1,500/mm3 Grade 3: ≥500- < 1,000/mm3 Grade 4: <500/mm3
| From screening to 28 days follow-up, an average 6 months |
| Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Treatment-emergent abnormalities in blood chemistry at any grade are presented by dose level. ALP = Alkaline phosphatase ALT = Alanine aminotransferase AST = Aspartate aminotransferase GGT = Gamma-glutamyl transferase LDH = Lactate dehydrogenase | From screening to 28 days follow-up, an average 6 months |
| Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Treatment Emergent abnormalities by dose Level are presented for blood chemistry and coagulation parameters. INR = international normalized ratio LNL = lower normal limit NL = normal limit ULN = upper limit of normal | From screening to 28 days follow-up, an average 6 months |
| Electrocardiogram Abnormalities | The number of participants who experienced electrocardiogram abnormalities are presented. | From screening to 28 days follow-up, an average 6 months |
| Tmax and Tlast of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Tmax = Time to maximum observed plasma concentration Tlast = Time of last detectable concentration | Day 1 to Day 15 |
| Cmax and Clast of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Cmax = Maximum observed plasma concentration Clast = Last detectable concentration | Day 1 to Day 15 |
| AUClast, AUCweekly, and AUCinf of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. AUClast = Area under the interpolated observed plasma time-concentration curve from infusion start to the last observed plasma concentration AUCweekly = Area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours AUCinf = Area under the interpolated observed plasma time-concentration curve from infusion start extrapolated to infinity based on the last observed plasma concentration | From Days 1 to 21 (168 hours after the Day 15 infusion) |
| t½,z of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. t½,z = Half-life of the terminal phase of observed plasma concentration | Day 1 to Day 15 |
| CL and CLss of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. CL = Clearance based on last observed concentration and extrapolation to infinity CLss = Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state | Day 1 to Day 15 |
| Vss and Vss,SS of NMS-01940153E | Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Vss = Volume of distribution at steady state based last observed concentration extrapolated to infinity and Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state Vss,SS = Volume of distribution at steady state based last observed concentration extrapolated to infinity and clearance based on last observed concentration and extrapolation to infinity | Day 1 to Day 15 |
| RA AUCweekly and RA Cmax of NMS-01940153E | Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. RA AUCweekly = Accumulation ratio Day 1 to 15 calculated using area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours RA Cmax = Accumulation ratio Day 1 to 15 calculated using maximum observed plasma concentration | Day 21 (168 hours after the Day 15 infusion) |
| FE of NMS-01940153E | Urine pharmacokinetic profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. FE = Molar fraction of excreted compound relative to the administered molar dose calculated using urine concentration and volume data | Day 1 to Day 15 |
| Phase I Objective Tumor Response (Partial and Complete Response) | Phase I any dose level, objective response and best overall tumor response are presented, as measured by investigator assessed RECIST 1.1 (Phase I). The objective response rate was calculated as the proportion of evaluable patients who achieved best overall response (BOR), confirmed complete response (CR) or partial response (PR). | Phase I: From the Study Start Date to Phase I Completion (32 months) |
| Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Objective response rate as measured by investigator-assessed mRECIST in Phase II. | Phase II: From Phase II start to Study Completion (23 months) |
| Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1 | Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1. Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response. | Phase I: From the Study Start Date to Phase I Completion (32 months) |
| Phase II: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1. and Investigator-assessed mRECIST | Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1 and investigator-assessed modified RECIST (mRECIST). Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response. | Phase II: From Phase II start to Study Completion (23 months) |
| Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II | Progression Free Survival as measured by investigator assessed RECIST 1.1, for all treated participants in Phase I and Phase II. Phase 2 started before Phase 1 completed. | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
| Overall Survival in Phases I and II | Overall Survival for all treated participants in Phases I and II. The estimates are based on the Kaplan-Meier (KM) method. Phase 2 started before Phase 1 completed. | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
| St Louis |
| Missouri |
| 63110-1032 |
| United States |
| Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | 20133 | Italy |
| Azienda Sanitaria Locale Napoli 1 Centro - Ospedale del Mare | Naples | 80145 | Italy |
| Istituto Oncologico Veneto - IRCCS | Padova | 35128 | Italy |
| Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara | Pisa | 56126 | Italy |
| Istituto Clinico Humanitas | Rozzano | 20089 | Italy |
| Azienda Ospedaliera Ordine Mauriziano di Torino | Torino | 10128 | Italy |
| Hospital Clínic de Barcelona | Barcelona | 8036 | Spain |
| FG002 | Phase II Participants: 100 mg/m2/Week | All participants in Phase II who received 100 mg/m2/week intravenous NMS-01940153E. |
| FG003 | Enrolled But Not Treated | Participants who were enrolled but not randomized and did not receive treatment. |
| COMPLETED | All participants who completed the study were followed up until death. |
|
| NOT COMPLETED |
|
|
All treated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I Participants: 100 mg/m2/Week | All participants in Phase I who received 100 mg/m2/week intravenous NMS-01940153E |
| BG001 | Phase I Treated Participants: 135 mg/m2/Week | All participants in Phase I who received 135 mg/m2/week intravenous NMS-01940153E |
| BG002 | Phase II Participants: 100 mg/m2/Week | All participants in Phase II who received 100 mg/m2/week intravenous NMS-01940153E |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| 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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| Race (NIH/OMB) | Count of Participants | Participants |
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| Eastern cooperative oncology group performance status | ECOG PS 0 = Fully active, able to carry on all pre-disease performance without restriction ECOG PS 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work | Number | participants |
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| 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 | Phase I Drug Related Dose Limiting Toxicities (DLTs) | All 12 Phase I treated patients were evaluable for DLT (Dose-Limiting Toxicity Evaluable Set) and included 6 patients treated at each of the two dose levels explored (i.e., 100 mg/m2/week and 135 mg/m2/week) who received at least 66% of the study drug in the first 28-day cycle of treatment and underwent a DLT assessment within the DLT window. Participants who experienced DLTs are presented. | Phase I treated participants | Posted | Count of Participants | Participants | Phase I: From screening to end of first 28-day cycle (17 months) |
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| Primary | Phase II Objective Response Rate | The objective response rate (ORR) was calculated as the proportion of evaluable patients who achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) measured by investigator-assessed RECIST 1.1 (Phase II). | Evaluable population | Posted | Count of Participants | Participants | Phase II: From Phase II start to Study Completion (23 months) |
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| Secondary | Treatment-emergent Adverse Events by Maximum CTC Grade | The maximum Common Terminology Criteria (CTC) grade (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. | All treated participants | Posted | Count of Participants | Participants | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
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| Secondary | Treatment-emergent Adverse Events Related to NMS-01940153E | The number of treatment-emergent adverse events related to NMS-01940153E by maximum CTC grade experienced (graded using NCI CTCAE Version 5.0). Whether the the AE was related or not was assessed by the investigator. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening. Phase 2 started before Phase 1 completed. | All treated participants | Posted | Number | events | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
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| Secondary | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Number of treatment emergent abnormalities (at any grade) at all dose levels are presented. CTC = Common Terminology Criteria WBC = white blood cells | All treated participants | Posted | Number | events | From screening to 28 days follow-up, an average 6 months |
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| Secondary | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | The mean days to first occurrence of neutrophil count decrease are presented for all dose levels. Grade 0: ≥2,000/mm3 Grade 1: ≥1,500-< 2,000/mm3 Grade 2: ≥1,000- < 1,500/mm3 Grade 3: ≥500- < 1,000/mm3 Grade 4: <500/mm3
| Only participants who experienced G3 or G4 were analyzed. | Posted | Mean | Standard Deviation | days | From screening to 28 days follow-up, an average 6 months |
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| Secondary | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Treatment-emergent abnormalities in blood chemistry at any grade are presented by dose level. ALP = Alkaline phosphatase ALT = Alanine aminotransferase AST = Aspartate aminotransferase GGT = Gamma-glutamyl transferase LDH = Lactate dehydrogenase | All treated participants | Posted | Number | events | From screening to 28 days follow-up, an average 6 months |
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| Secondary | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Treatment Emergent abnormalities by dose Level are presented for blood chemistry and coagulation parameters. INR = international normalized ratio LNL = lower normal limit NL = normal limit ULN = upper limit of normal | All treated participants | Posted | Number | events | From screening to 28 days follow-up, an average 6 months |
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| Secondary | Electrocardiogram Abnormalities | The number of participants who experienced electrocardiogram abnormalities are presented. | All treated participants | Posted | Count of Participants | Participants | From screening to 28 days follow-up, an average 6 months |
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| Secondary | Tmax and Tlast of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Tmax = Time to maximum observed plasma concentration Tlast = Time of last detectable concentration | All Phase I participants | Posted | Mean | Standard Deviation | hours | Day 1 to Day 15 |
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| Secondary | Cmax and Clast of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Cmax = Maximum observed plasma concentration Clast = Last detectable concentration | All Phase I participants | Posted | Mean | Standard Deviation | μM | Day 1 to Day 15 |
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| Secondary | AUClast, AUCweekly, and AUCinf of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. AUClast = Area under the interpolated observed plasma time-concentration curve from infusion start to the last observed plasma concentration AUCweekly = Area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours AUCinf = Area under the interpolated observed plasma time-concentration curve from infusion start extrapolated to infinity based on the last observed plasma concentration | All Phase I participants | Posted | Mean | Standard Deviation | h·μM | From Days 1 to 21 (168 hours after the Day 15 infusion) |
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| Secondary | t½,z of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. t½,z = Half-life of the terminal phase of observed plasma concentration | All Phase I participants | Posted | Mean | Standard Deviation | days | Day 1 to Day 15 |
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| Secondary | CL and CLss of NMS-01940153E | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. CL = Clearance based on last observed concentration and extrapolation to infinity CLss = Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state | All Phase I participants | Posted | Mean | Standard Deviation | L/h | Day 1 to Day 15 |
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| Secondary | Vss and Vss,SS of NMS-01940153E | Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Vss = Volume of distribution at steady state based last observed concentration extrapolated to infinity and Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state Vss,SS = Volume of distribution at steady state based last observed concentration extrapolated to infinity and clearance based on last observed concentration and extrapolation to infinity | All Phase I participants | Posted | Mean | Standard Deviation | L | Day 1 to Day 15 |
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| Secondary | RA AUCweekly and RA Cmax of NMS-01940153E | Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. RA AUCweekly = Accumulation ratio Day 1 to 15 calculated using area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours RA Cmax = Accumulation ratio Day 1 to 15 calculated using maximum observed plasma concentration | All Phase I participants | Posted | Mean | Standard Deviation | ratio | Day 21 (168 hours after the Day 15 infusion) |
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| Secondary | FE of NMS-01940153E | Urine pharmacokinetic profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. FE = Molar fraction of excreted compound relative to the administered molar dose calculated using urine concentration and volume data | All treated participants | Posted | Mean | Standard Deviation | percentage | Day 1 to Day 15 |
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| Secondary | Phase I Objective Tumor Response (Partial and Complete Response) | Phase I any dose level, objective response and best overall tumor response are presented, as measured by investigator assessed RECIST 1.1 (Phase I). The objective response rate was calculated as the proportion of evaluable patients who achieved best overall response (BOR), confirmed complete response (CR) or partial response (PR). | Treated Patients with at Least One RECIST 1.1 On-Treatment Assessment | Posted | Count of Participants | Participants | Phase I: From the Study Start Date to Phase I Completion (32 months) |
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| Secondary | Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Objective response rate as measured by investigator-assessed mRECIST in Phase II. | Evaluable participants with at least one mRECIST Assessment on Treatment were analyzed | Posted | Count of Participants | Participants | Phase II: From Phase II start to Study Completion (23 months) |
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| Secondary | Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1 | Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1. Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response. | Phase I participants who experienced partial response | Posted | Number | months | Phase I: From the Study Start Date to Phase I Completion (32 months) |
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| Secondary | Phase II: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1. and Investigator-assessed mRECIST | Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1 and investigator-assessed modified RECIST (mRECIST). Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response. | Phase II Evaluable Population. No participants had a RECIST or mRECIST complete or partial response observed. | Posted | Phase II: From Phase II start to Study Completion (23 months) |
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| Secondary | Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II | Progression Free Survival as measured by investigator assessed RECIST 1.1, for all treated participants in Phase I and Phase II. Phase 2 started before Phase 1 completed. | All evaluable participants | Posted | Median | 95% Confidence Interval | months | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
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| Secondary | Overall Survival in Phases I and II | Overall Survival for all treated participants in Phases I and II. The estimates are based on the Kaplan-Meier (KM) method. Phase 2 started before Phase 1 completed. | Evaluable population | Posted | Median | 95% Confidence Interval | months | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) |
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Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months). Phase 2 started before Phase 1 completed.
Adverse events were coded by MedDRA and severity was graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
For non-serious AEs, the number of participants who experienced at least 1 occurrence of a treatment-emergent non-serious AEs, by MedDRA System Organ Class and Preferred Term are presented.
The one participant who was enrolled but not treated was not assessed for adverse events and therefore this cohort has not been included.
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 | Phase I: 100 mg/m2/Week | All participants in Phase I who received 100 mg/m2/week intravenous NMS-01940153E | 5 | 6 | 1 | 6 | 5 | 6 |
| EG001 | Phase I: 135 mg/m2/Week | All participants in Phase I who received 135 mg/m2/week intravenous NMS-01940153E | 5 | 6 | 2 | 6 | 6 | 6 |
| EG002 | Phase II: 100 mg/m2/Week | All participants in Phase II who received 100 mg/m2/week intravenous NMS-01940153E | 9 | 18 | 5 | 18 | 18 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Device related bacteraemia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Peritonitis bacterial | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (23.1) | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA (23.1) | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Asthenia | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Infusion site reaction | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Infusion site pain | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Haemoperitoneum | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Chromaturia | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
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| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
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| Hyperthyroidism | Endocrine disorders | MedDRA (23.1) | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA (23.1) | Systematic Assessment |
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| Melaena | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Peptic ulcer | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Tooth loss | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Infusion site extravasation | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Infusion site phlebitis | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Infusion site pruritus | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Acarodermatitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Burn infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Oral fungal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Adverse event following immunisation | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Coronavirus test positive | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
In the Phase II part of the study, among the patients evaluable for efficacy, no objective response (partial response or clinical response) was observed at the first futility analysis. Therefore, this study was terminated for clinical futility, according to the protocol rules.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alberto Ocana | Nerviano Medical Sciences S.r.l. | 39 0331 58 1111 | DL-Clinicaltrials@nervianoms.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 30, 2023 | Feb 19, 2025 | SAP_003.pdf |
Not provided
| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| ECOG Performance Status 1 |
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| OG002 | Phase II (Evaluable Population) | All participants in Phase II who received 100 mg/m2/week intravenous NMS-01940153E in the Evaluable Population. The Evaluable Population was participants of the treated set who had measurable disease at baseline assessed according to RECIST 1.1 and at least one tumor evaluation on treatment, unless they died before the first tumor on-treatment assessment, in which case they were considered treatment failure. |
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| Phase II (Evaluable Population) |
All participants in Phase II who received 100 mg/m2/week intravenous NMS-01940153E in the Evaluable Population. The Evaluable Population was participants of the treated set who had measurable disease at baseline assessed according to RECIST 1.1 and at least one tumor evaluation on treatment, unless they died before the first tumor on-treatment assessment, in which case they were considered treatment failure. |
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