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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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.
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.
Please Contact U.S. Medical Information
Rockland, Massachusetts, United States
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.
Time frame: Baseline up to Day 21
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.
Time frame: 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.
Time frame: Screening up to 28 days after last dose of drug; assessed up to maximum of 1.41 years
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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 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.
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).