Study to Investigate DRP-104 in Adults With Advanced Solid Tumors

This study will be conducted in 4 Parts: Part 1: Phase 1 single-agent dose escalation of DRP-104 administered via IV infusion (Cohort 1a) or subQ injection (Cohort 1b and 1c) in patients with advanced solid tumors (excluding primary CNS tumors and HCC): 1. Cohort 1a: IV DRP-104 dose escalation to define the IV MTD/MAD/RP2D (up to approximately 50 patients) 2. Cohort 1b: subQ twice weekly DRP-104 dose escalation to define the twice weekly subQ MTD/MAD/RP2D (up to approximately 50 patients) 3. Cohort 1c: subQ thrice weekly DRP-104 dose escalation to define the thrice weekly subQ MTD/MAD/RP2D (up to approximately 12 patients) Upon completion of Part 1, Cohort 1a, 1b, and 1c, the recommended phase 2 route of administration (RP2R: IV or subQ) and schedule of administration (RP2S: twice or thrice weekly) and corresponding MTD/MAD/RP2D will be determined prior to starting Part 2, cohort 2. As of Version 5 of the protocol, further assessment of the intravenous formulation was terminated prior to declaring MTD/MAD/RP2D and the RP2R was determined to be subQ (Section 2.5.5). Part 2, which opens to enrollment once the MTD/MAD/RP2D/RP2R of DRP-104 has been declared from either Part 1-Cohort 1a, 1b, or 1c and/or the RP2R/RP2S has been determined from Part 1 and includes 2 specific cohorts: 1. Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled. 2. Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2. Part 3: Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients); The dose of atezolizumab is fixed. Enrollment for Part 3 will begin once at least 14 patients from either Part 1 or 2 have been treated at this dose, route, and schedule for at least one cycle to ensure safety. Part 4: Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients).