Primary Outcome Measures
- Phase 1: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [ Time Frame: Screening through 60 days after end of treatment, up to 18 months ]
A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment. - Phase 2: Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months ]Defined as the percentage of subjects having complete response (CR) or partial response (PR).
- Phase 2: Complete response rate (CRR) based on RECIST v1.1 [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months ] Defined as the percentage of checkpoint inhibitor-naive melanoma subjects who have a CR.
Secondary Measures
- Phase 1 & Phase 2: ORR based on RECIST v1.1 and mRECIST [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months ] Defined as the percentage of subjects having CR or PR.
- Phase 1 & Phase 2: Disease control rate based on RECIST v1.1 and mRECIST [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months. ]Defined as the percentage of subjects having CR, PR, or stable disease (SD).
- Phase 1 & Phase 2: Duration of response based on RECIST v1.1 and mRECIST [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months ]
Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause. - Phase 1 & Phase 2: Duration of disease control based on RECIST v1.1 and mRECIST [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months ] Defined as time from first report of SD or better until disease progression or death from any cause.
- Phase 1 & Phase 2: Progression-free survival based on RECIST v1.1 and mRECIST [ Time Frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months ] Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
- Phase 1 & Phase 2: Overall survival [ Time Frame: At 1 year and 2 years. ] Defined as the time from the start of combination therapy until death due to any cause.
- Phase 1 & Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [ Time Frame: Screening through 60 days after end of treatment, up to 18 months. ]
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
Eligibility
- Inclusion Criteria
- Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
- Phase 1: Subjects with advanced or metastatic solid tumors.
- Phase 1: Subjects who have disease progression after treatment with available therapies.
- Phase 2: Subjects with advanced or metastatic melanoma, RCC, and urothelial carcinoma.
- Presence of measurable disease based on RECIST v1.1.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Exclusion Criteria
- Laboratory and medical history parameters not within the Protocol-defined range
- Prior treatment with an immune therapy.
- Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
- Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.
- Active autoimmune disease.
- Known active central nervous system metastases and/or carcinomatous meningitis.
- Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
- Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
- Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
