Phase II Study of Anti-PD-1/VEGF Bispecific Antibody Ivonescimab in Patients With Previously Treated Metastatic Colorectal Cancer

Required: MLH1 deficient mismatch repair

dMMR or MSI-H per local testing (Cohort 1)

Required: MSH2 deficient mismatch repair

dMMR or MSI-H per local testing (Cohort 1)

Required: MSH6 deficient mismatch repair

dMMR or MSI-H per local testing (Cohort 1)

Required: PMS2 deficient mismatch repair

dMMR or MSI-H per local testing (Cohort 1)

Required: MSI high microsatellite instability

dMMR or MSI-H per local testing (Cohort 1)

Required: MLH1 proficient mismatch repair

pMMR or non-MSI-H per local testing (Cohorts 2 and 3)

Required: MSH2 proficient mismatch repair

pMMR or non-MSI-H per local testing (Cohorts 2 and 3)

Required: MSH6 proficient mismatch repair

pMMR or non-MSI-H per local testing (Cohorts 2 and 3)

Required: PMS2 proficient mismatch repair

pMMR or non-MSI-H per local testing (Cohorts 2 and 3)

Required: MSI microsatellite stable

pMMR or non-MSI-H per local testing (Cohorts 2 and 3)

Required: KRAS extended RAS status known

Known extended RAS and BRAF status as per local standard of practice (Cohorts 2 and 3 only)

Required: NRAS extended RAS status known

Known extended RAS and BRAF status as per local standard of practice (Cohorts 2 and 3 only)

Required: BRAF status known

Known extended RAS and BRAF status as per local standard of practice (Cohorts 2 and 3 only)

Must have received: immune checkpoint inhibitor (anti-PD-1, anti-CTLA-4) — MSI-H/dMMR cohort only

Demonstrated radiographic or clinical disease progression following treatment with immune checkpoint inhibitors including anti-PD-1 +/- anti-CTLA-4 therapy. Must have received at least 2 doses of a PD1/PD-L1 inhibitor. Progressive disease either during therapy or within 3 months of last dose of therapy.

Must have received: fluoropyrimidine — Cohorts 2 and 3 only

Participant must have progressed (radiologically or clinically) or been intolerant to fluoropyrimidine, irinotecan, and oxaliplatin (Cohorts 2 and 3 only)

Must have received: irinotecan — Cohorts 2 and 3 only

Participant must have progressed (radiologically or clinically) or been intolerant to fluoropyrimidine, irinotecan, and oxaliplatin (Cohorts 2 and 3 only)

Must have received: oxaliplatin — Cohorts 2 and 3 only

Participant must have progressed (radiologically or clinically) or been intolerant to fluoropyrimidine, irinotecan, and oxaliplatin (Cohorts 2 and 3 only)

Cannot have received: immune checkpoint inhibitor (PD-1, PD-L1, CTLA-4)

Exception: MSI-H/dMMR tumors

Except for MSI-H/dMMR tumors, prior therapy with PD-1, PD-L1, or CTLA-4 inhibitors (Cohorts 2 and 3 only).