Clinical Trials

Inclusion Criteria:

• Female patients must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication if of childbearing potential or be of nonchildbearing potential.
• Female patients of childbearing potential (see above) must agree to use 2 adequate methods of contraception with their partner.
• ECOG performance status of ≤1.
• Adequate hematologic and organ function.

Exclusion Criteria:

• For Part 1a: anti-CTLA-4, anti-PD-1, anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent within 3 weeks (ie, 21 days) prior to initiation of study treatment.
• For Parts 1b,1c and 1d: anti-CTLA-4 within 3 weeks (i.e., 21 days) prior to initiation of study treatment and/or prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIM-3 or anti-LAG-3 agent that resulted in permanent discontinuation due to an AE.
• For Part 1e: prior treatment with anti-PD-1, anti-PD-L1, anti-TIM-3 or anti-LAG-3.
• For Part 2 combination arm/s (TSR-022 + TSR-042): prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE; prior treatment with an anti LAG-3 or anti TIM-3 is also excluded
• Known uncontrolled central nervous system (CNS) metastases and/or carcinomatousmeningitis.
• Other serious, uncontrolled medical disorders including, but not limited to nonmalignant systemic disease or active infection requiring systemic therapy, immunodeficiency, known history of human immunodeficiency virus (HIV) infection or HIV 1/2 antibodies, known active hepatitis B, active autoimmune disease, history of interstitial lung disease, history of ≥Grade 3immune-related AE with prior immunotherapy with the exception of non-clinically significant lab abnormalities.
• History of pneumonitis.
• History of ≥Grade 3 immune-related AE with prior immunotherapy with the exception of non-clinically significant lab abnormalities.
  • Note (for all patients except Part 1e):
    • Patient may be considered eligible if anti PD-1/PD-L1 antibody treatment was tolerated without corticosteroids or other immunosuppressive therapy following a Grade 3 irAE on prior anti-CTLA-4 therapy.
• Pregnant or breast feeding, or expecting to conceive children within the projected duration of the study.
• Not recovered (i.e., to ≤ Grade 1 or to baseline) from treatment-related AEs.
• Participation in an investigational study (therapy or device) within 4 weeks prior to start of study treatment.
• Prior anticancer therapy within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter.
• Incomplete recovery from AEs and/or major surgery (must be (≤ Grade 1).
• Received a vaccine within 7 days of planned start of study therapy.
• Has a known hypersensitivity to TSR-022, TSR-042, TSR-033 or to nivolumab (if applicable) components or excipients.