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The study is terminated prematurely as the sponsor decided to discontinue program of NHS-IL2 [MSB0010445]
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
This is a Phase 2a, open-label, parallel group, partly randomized dose escalation trial to assess the safety and efficacy of a low dose, an intermediate dose, and high dose MSB0010445 given by intravenous infusion to subjects with advanced (unresectable or metastatic) melanoma in combination with stereotactic body radiation therapy (SBRT).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MSB0010445 Low Dose Cohort 0.3 mg/kg | Experimental |
| |
| MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | Experimental |
| |
| MSB0010445 High Dose Cohort 1.8 mg/kg | Experimental |
| |
| MSB0010445 High Dose Cohort 2.4 mg/kg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MSB0010445 (0.3 milligram per kilogram [mg/kg]) | Drug | MSB0010445 will be administered at a single dose of 0.3 mg/kg as intravenous (IV) infusion over approximately 1 hour every 3 weeks (q3w) for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of Stereotactic Body Radiation Therapy (SBRT) to the targeted reference lesion. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT) | DLT was defined as any Grade>= 3 toxicity related to drug, occurring during 21 days post first dose of drug except Grade 3 infusion-related adverse reaction resolving within 6 hours and Transient (<=6 hours) Grade 3 flu-like symptoms/fever controlled with medical management; Transient (<= 24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to <= Grade 1; Grade 3 skin toxicity ,Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 8 x upper limit of normal (ULN)/total bilirubin < 5 x ULN resolving to <= Grade 1 in <7 days after medical management; Grade 3 diarrhea controlled with maximal medical management within 72 hours; Grade 4 lymphopenia that resolves to <= Grade 1 within 7 days & with no clinical manifestations; Grade 3 lab abnormality with no clinical correlation and resolves to <= Grade 1 within 7 days with adequate medical management Tumor flare defined as local pain, irritation or rash localized at sites of known/suspected tumor. | Baseline up to Day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | BOR was defined as a confirmed complete response (CR) or partial response (PR) during second-line treatment. For target lesions (TLs), CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. |
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Inclusion Criteria:
Advanced unresectable or metastatic melanoma, previously treated with ipilimumab; anti-melanoma treatments, including anti-PD/PD-L1 or any other immunotherapy, are allowed provided no treatment from last dose of that treatment to trial enrolment
Subjects need to have
The lesion that is biopsied at Baseline can be the lesion that will be irradiated
The lesion that will be biopsied while on treatment should not be a lesion that has been irradiated or biopsied at Baseline
Signed written informed consent
Male and female subjects at least 18 years of age
Life expectancy greater than or equal to (>=) 4 months
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
Other protocol defined inclusion criteria could apply
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Please Contact U.S. Medical Information | Rockland | Massachusetts | United States |
Not provided
First/Last subject (informed consent): 24 January 2014/17 December 2014. Study completion date:10 June 2015. The study was conducted at 6 sites in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | MSB0010445 Low Dose Cohort 0.3 mg/kg | MSB0010445 was administered at a single dose of 0.3 mg/kg as intravenous (IV) infusion over approximately 1 hour every 3 weeks (q3w) for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of Stereotactic Body Radiation Therapy (SBRT) to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions if one site was targeted subject received 3 fractions (1 per day) of 8 Gray (Gy) each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| FG001 | MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | MSB0010445 was administered at a single dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| FG002 | MSB0010445 High Dose Cohort 1.8 mg/kg | MSB0010445 was administered at a single dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| FG003 | MSB0010445 High Dose Cohort 2.4 mg/kg | MSB0010445 was administered at a single dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety analyst set included all subjects who signed informed consent, were enrolled into the study and received at least 1 dose of MSB0010445.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | MSB0010445 Low Dose Cohort 0.3 mg/kg | MSB0010445 was administered at a dose of 0.3 mg/kg as IV infusion over approximately 1 hour q3w until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. One site was targeted and was received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose was 18 Gy (3 x 6 Gy). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT) | DLT was defined as any Grade>= 3 toxicity related to drug, occurring during 21 days post first dose of drug except Grade 3 infusion-related adverse reaction resolving within 6 hours and Transient (<=6 hours) Grade 3 flu-like symptoms/fever controlled with medical management; Transient (<= 24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to <= Grade 1; Grade 3 skin toxicity ,Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 8 x upper limit of normal (ULN)/total bilirubin < 5 x ULN resolving to <= Grade 1 in <7 days after medical management; Grade 3 diarrhea controlled with maximal medical management within 72 hours; Grade 4 lymphopenia that resolves to <= Grade 1 within 7 days & with no clinical manifestations; Grade 3 lab abnormality with no clinical correlation and resolves to <= Grade 1 within 7 days with adequate medical management Tumor flare defined as local pain, irritation or rash localized at sites of known/suspected tumor. | Safety analysis set included all subjects who signed informed consent, were enrolled into the study and received at least 1 dose of MSB0010445. | Posted | Number | subjects | Baseline up to Day 21 |
Signing of the informed consent up to 1.41 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MSB0010445 Low Dose Cohort 0.3 mg/kg | MSB0010445 was administered at a single dose of 0.3 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 18.0 | Non-systematic Assessment |
The study was terminated early due to sponsor's decision to discontinue the development of MSB0010445. The decision to discontinue development of MSB0010445 was not related to any safety or efficacy concerns.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@merckgroup.com |
Not provided
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
Not provided
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
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|
| MSB0010445 (1.0 mg/kg) | Drug | MSB0010445 will be administered at a single dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion. |
|
| MSB0010445 (1.8 mg/kg) | Drug | MSB0010445 will be administered at a single dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion. |
|
| MSB0010445 (2.4 mg/kg) | Drug | MSB0010445 will be administered at a single dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 will be performed 3 days after the last dose of SBRT to the targeted reference lesion. |
|
| Stereotactic Body Radiation Therapy (SBRT) | Radiation | SBRT will be administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions if one site will be targeted subject received 3 fractions (1 per day) of 8 Gray (Gy) each (total: 24 Gy). If the target lesion will be located in the thorax, the maximum total dose administered will be 18 Gy (3 x 6 Gy). |
|
| Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years |
| Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs | TEAE was defined as an AE that started on or after the first administration of SBRT. An SAE was 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. | Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years |
| BG001 | MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | MSB0010445 was administered at a dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. One site was targeted and was received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose was 18 Gy (3 x 6 Gy). |
| BG002 | MSB0010445 High Dose Cohort 1.8 mg/kg | MSB0010445 was administered at a dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. One site was targeted and was received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose was 18 Gy (3 x 6 Gy). |
| BG003 | MSB0010445 High Dose Cohort 2.4 mg/kg | MSB0010445 was administered at a dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. One site was targeted and was received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose was 18 Gy (3 x 6 Gy). |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | MSB0010445 Low Dose Cohort 0.3 mg/kg | MSB0010445 was administered at a single dose of 0.3 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| OG001 | MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | MSB0010445 was administered at a single dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| OG002 | MSB0010445 High Dose Cohort 1.8 mg/kg | MSB0010445 was administered at a single dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
| OG003 | MSB0010445 High Dose Cohort 2.4 mg/kg | MSB0010445 was administered at a single dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). |
|
|
| Secondary | Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | BOR was defined as a confirmed complete response (CR) or partial response (PR) during second-line treatment. For target lesions (TLs), CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. | Safety analysis set included all subjects who signed informed consent, were enrolled into the study and received at least 1 dose of MSB0010445. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure. | Posted | Number | subjects | Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years |
|
|
|
| Secondary | Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs | TEAE was defined as an AE that started on or after the first administration of SBRT. An SAE was 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. | Safety analysis set included all subjects who signed informed consent, were enrolled into the study and received at least 1 dose of MSB0010445. | Posted | Number | subjects | Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years |
|
|
|
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | MSB0010445 Intermediate Dose Cohort 1.0 mg/kg | MSB0010445 was administered at a single dose of 1.0 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). | 0 | 2 | 2 | 2 |
| EG002 | MSB0010445 High Dose Cohort 1.8 mg/kg | MSB0010445 was administered at a single dose of 1.8 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). | 3 | 6 | 6 | 6 |
| EG003 | MSB0010445 High Dose Cohort 2.4 mg/kg | MSB0010445 was administered at a single dose of 2.4 mg/kg as IV infusion over approximately 1 hour q3w for the first 12 Weeks as a part of induction phase followed by maintenance dose of 0.3 mg/kg drug every three weeks until significant clinical progression, occurrence of unacceptable toxicity, or withdrawal of consent. The first administration of MSB0010445 was performed 3 days after the last dose of SBRT to the targeted reference lesion. SBRT was administered using a dose and schedule recommended based upon the data showing the best abscopal effect using multiple fractions. If one site was targeted subject received 3 fractions (1 per day) of 8 Gy each (total: 24 Gy). If the target lesion was located in the thorax, the maximum total dose administered was 18 Gy (3 x 6 Gy). | 1 | 2 | 2 | 2 |
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Cardiomyopathy | Cardiac disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 18.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Depressive symptom | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Xeroderma | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dyspnoea at rest | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Capillary leak syndrome | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA 18.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Conjunctival Irritation | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Radiation associated pain | Injury, poisoning and procedural complications | MedDRA 18.0 | Non-systematic Assessment |
|
| Peripheral coldness | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Early satiety | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D013514 |
| Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| PR |
|
| Serious AEs |
|