Mass General - Division of Clinical Research

Disease Criteria - - Part 1A and 1C: Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard therapy, or standard therapy is not curative or available; - Part 1B: - Any histologically or cytologically confirmed solid tumor malignancy for which anti-PD-1 or anti-PD-L1 treatment is approved and has progressed on or after prior anti-PD-1 or anti-PD-L1 therapy. - Patients with metastatic castrate-resistant prostate cancer if they have progressed on at least 2 lines of systemic therapy - Patients with extensive stage small cell lung cancer (SCLC) after at least 1 line of prior therapy - Patients with microsatellite stable colorectal cancer after at least 2 lines of prior therapy - Phase 2: Patients with histologically confirmed metastatic MSS CRC are eligible to enroll in Phase 2 as follows: - Patients must have had at least 1 prior chemotherapy regimen for metastatic CRC including all of the following agents: a fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab or biosimilars, an anti epidermal growth factor receptor antibody (cetuximab or panitumumab), and v-raf murine sarcoma viral oncogene homolog B1 inhibitor/BRAF (encorafenib), if applicable - Patients with MSI-H/dMMR are excluded - ECOG performance status of 0 or 1 - Adequate organ function - Part 1B, Part 1C, and Phase 2 only: measurable disease per iRECIST

• Received prior treatment with anti-CTLA-4 therapy - Received prior immune-checkpoint therapy and experienced Grade 3 or greater toxicity lasting greater than 6 weeks - Received prior approved systemic anticancer therapy within 4 weeks prior to study treatment - Received prior radiotherapy within 2 weeks prior to study treatment - Phase 2 only: Received prior anti-PD-1/L1 therapy or any investigational checkpoint inhibitory therapy - Has a diagnosis of immunodeficiency - Has known malignancy (other than disease under study) that is progressing or has required active treatment within the past 3 years - Has an active autoimmune disease that has required systemic treatment in past 2 years, including the use of disease modifying agents, corticosteroids or immunosuppressive drugs - Has an active infection requiring systemic intravenous therapy within 4 weeks prior to study treatment, or oral therapy within 2 weeks prior to study treatment - Has a history of severe hypersensitivity reaction (≥ Grade 3) to any study intervention and/or any of its excipients - Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study - Phase 2 only: symptomatic bowel obstruction