MSB0010445 and Stereotactic Body Radiation Therapy in Advanced Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: MSB0010445 (0.3 milligram per kilogram [mg/kg]); MSB0010445 (1.0 mg/kg); MSB0010445 (1.8 mg/kg); MSB0010445 (2.4 mg/kg); Stereotactic Body Radiation Therapy (SBRT)
Intervention description: 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.; 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).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; MSB0010445; Dose limiting toxicity; Stereotactic body radiation therapy

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).
    

Eligibility criteria:

        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