Study of Zanzalintinib in Combination With Immuno-Oncology or Other Agents in Participants With Solid Tumors

Required: PD-L1 (CD274) expression (TPS 1-49%)

Expansion Cohort 8 (NSCLC): ...positive PD-L1 expression (tumor proportion score [TPS] 1-49%)

Required: PD-L1 (CD274) expression (CPS ≥1)

Expansion Cohort 11 (HNSCC): ...PD-L1 combined positive score (CPS) ≥1.

Must have received: PD-1/PD-L1 inhibitor with VEGFR-TKI or CTLA-4 mAb — Expansion Cohort 2 (ccRCC)

Must have radiographically progressed after a combination therapy consisting of a Programmed Cell Death Protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) targeting monoclonal antibody (mAb) with a Vascular endothelial growth factor (receptor) tyrosine kinase inhibitor (VEGFR-TKI) or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.

Must have received: novel hormone therapy — Expansion Cohort 3 (mCRPC)

Must have progressed during or after one novel hormone therapy (NHT) given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.

Must have received: platinum-based chemotherapy — Expansion Cohort 4 (UC, ICI-naive)

Must have progressed during or after prior first-line platinum-based combination therapy, including participants who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.

Must have received: immune checkpoint inhibitor (anti-PD-1, anti-PD-L1) — Expansion Cohort 9 (NSCLC)

Expansion Cohort 9 (NSCLC): ...radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.

Cannot have received: zanzalintinib

Prior treatment with zanzalintinib

Cannot have received: nivolumab

Exception: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).

Prior treatment with ... nivolumab ... with the following exceptions: Prior PD-1/PD-L1, LAG-3 and cytotoxic T lymphocyte associated protein 4 (CTLA-4) targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).

Cannot have received: ipilimumab

Exception: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).

Prior treatment with ... ipilimumab ... with the following exceptions: Prior PD-1/PD-L1, LAG-3 and cytotoxic T lymphocyte associated protein 4 (CTLA-4) targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).

Cannot have received: relatlimab

Exception: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).

Prior treatment with ... relatlimab ... with the following exceptions: Prior PD-1/PD-L1, LAG-3 and cytotoxic T lymphocyte associated protein 4 (CTLA-4) targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).

Cannot have received: triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb

For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.

Cannot have received: taxane-based chemotherapy for mCRPC

For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.

Cannot have received: regorafenib and/or trifluridine + tipiracil (TAS-102) (regorafenib, trifluridine + tipiracil)

For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or trifluridine + tipiracil (TAS-102).