MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma

Phase 2

Terminated

Interventions: Drug: MSB0010445 (2.4 mg/kg)
Drug: MSB0010445 (0.3 milligram per kilogram [mg/kg])
Drug: MSB0010445 (1.0 mg/kg)
Drug: MSB0010445 (1.8 mg/kg)
Radiation: Stereotactic Body Radiation Therapy (SBRT)

Brief Summary: 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).

Recruitment & Eligibility

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
- one lesion that can be irradiated
- at least 1 measurable lesion outside the radiation field, different from the lesion that will be irradiated
- one lesion that can be biopsied before treatment with SBRT and MSB0010445
- one lesion outside the radiation field that can be biopsied while on treatment with MSB0010445
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

Active central nervous system metastasis
Treatment with systemic anti-cancer therapy within the 30 days before the first dose of SBRT
Pre-existing pericardial effusion or history of Grade >=2 pleural effusion or ascites within 3 months before first dose of SBRT
Concurrent systemic therapy with steroids or other immunosuppressive agents except short-term systemic steroids for allergic reactions
Other protocol defined exclusion criteria could apply

Arm && Interventions

Group	Intervention	Description
MSB0010445 Low Dose Cohort 0.3 mg/kg	Stereotactic Body Radiation Therapy (SBRT)	-
MSB0010445 High Dose Cohort 2.4 mg/kg	MSB0010445 (2.4 mg/kg)	-
MSB0010445 Low Dose Cohort 0.3 mg/kg	MSB0010445 (0.3 milligram per kilogram [mg/kg])	-
MSB0010445 Intermediate Dose Cohort 1.0 mg/kg	Stereotactic Body Radiation Therapy (SBRT)	-
MSB0010445 High Dose Cohort 2.4 mg/kg	Stereotactic Body Radiation Therapy (SBRT)	-
MSB0010445 Intermediate Dose Cohort 1.0 mg/kg	MSB0010445 (1.0 mg/kg)	-
MSB0010445 High Dose Cohort 1.8 mg/kg	MSB0010445 (1.8 mg/kg)	-
MSB0010445 High Dose Cohort 1.8 mg/kg	Stereotactic Body Radiation Therapy (SBRT)	-

Primary Outcome Measures

Name	Time	Method
Number of Subjects With at Least 1 Dose Limiting Toxicity (DLT)	Baseline up to Day 21	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.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Best Overall Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1	Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years	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.
Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious AEs	Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years	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.