Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patients With Advanced Cancer

This Phase 1 study will enroll up to approximately 200 evaluable adult patients with a histologically confirmed diagnosis of advanced cancer for which no standard therapy is available or standard therapy has failed, regardless of diagnosis and prior therapies. This also includes patients with PD-1/PD-L1 R/R melanoma. Patients may be enrolled into one of 5 treatment arms: 2-Week AGEN2373 monotherapy 3-Week AGEN2373 monotherapy 4-Week AGEN2373 monotherapy Combination of AGEN2373 and botensilimab in patients with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) relapsed/refractory (R/R) melanoma. Group 1 (Monotherapy Lead-in Combination): AGEN2373 will be administered every 3 weeks (Q3W). Starting on Cycle 4, AGEN1181 will be administered on Day 1 of every other 3-week cycle (Cycles 4, 6, 8, etc.) in combination with AGEN2373. Group 2 (Combination): AGEN2373 will be administered Q3W in combination with botensilimab administered every other cycle. The trial will consist of a 3+3 dose escalation that will evaluate different combination dose levels of AGEN2373 monotherapy and in combination with botensilimab. Each patient will stay on the dose level and schedule assigned at trial entry. Treatment with AGEN2373 monotherapy will be up to 2 years (i.e., maximum of 34 cycles). For combination therapy, AGEN1181 will be continued up to 1 year (i.e., maximum of 8 doses) and for AGEN2373 up to 2 years (i.e., maximum of 34 cycles), or until unacceptable toxicity, disease progression, consent is withdrawn, or any criterion for stopping the study drug or withdrawal of trial occurs. Patients who do not complete the DLT observation period (28 days for the 2-Week and 4-Week AGEN2373 Monotherapy arms and 21 days for the 3-Week AGEN2373 Monotherapy and Combination arms) after the first dose for reasons other than DLT will be replaced.