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

Required: PD-L1 (CD274) expression (tumor proportion score [TPS] 1-49%) (TPS 1-49%)

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

Required: PD-L1 (CD274) combined positive score (CPS) ≥1 (CPS ≥1)

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

Required: MSH2 microsatellite stable

Cohort 10 (CRC, microsatellite stable [MSS], 2L+)

Must have received: VEGFR inhibitor — adjuvant or neoadjuvant

Prior non-vascular endothelial growth factor (VEGF) targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.

Must have received: PD-1/PD-L1 inhibitor + VEGFR-TKI or PD-1 inhibitor + CTLA-4 inhibitor — preceding line of therapy

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 — castration-sensitive locally advanced or metastatic prostate cancer, M0 CRPC, or 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 — first-line or neoadjuvant/adjuvant

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) — metastatic disease

Participants with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.

Must have received: enfortumab vedotin (enfortumab vedotin)

Progressive disease following prior EV or ineligible for EV, and progression following prior PD-1/PD-L1 inhibitor or ineligible for PD-1/PD-L1 inhibitor.

Cannot have received: zanzalintinib (zanzalintinib)

Prior treatment with zanzalintinib

Cannot have received: nivolumab (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 zanzalintinib, nivolumab, ipilimumab or relatlimab with the following exceptions: ...

Cannot have received: ipilimumab (ipilimumab)

Exception: see above

Prior treatment with zanzalintinib, nivolumab, ipilimumab or relatlimab with the following exceptions: ...

Cannot have received: relatlimab (relatlimab)

Exception: see above

Prior treatment with zanzalintinib, nivolumab, ipilimumab or relatlimab with the following exceptions: ...

Cannot have received: small molecule kinase inhibitor

Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.

Cannot have received: anticancer antibody

Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.

Cannot have received: systemic chemotherapy

Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.

Cannot have received: abiraterone (abiraterone)

Receipt of abiraterone within 1 week

Cannot have received: cyproterone (cyproterone)

cyproterone within 10 days

Cannot have received: androgen receptor inhibitor (flutamide, nilutamide, bicalutamide, enzalutamide)

receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.

Cannot have received: taxane

Receipt of a taxane-based chemotherapy for mCRPC.

Cannot have received: regorafenib (regorafenib)

Receipt of prior therapy with regorafenib and/or trifluridine + tipiracil (TAS-102).

Cannot have received: trifluridine + tipiracil (trifluridine + tipiracil, TAS-102)

Receipt of prior therapy with regorafenib and/or trifluridine + tipiracil (TAS-102).