The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 (sirpiglenastat) administered via intravenous infusion or via subcutaneous injection as a single agent and in combination with atezolizumab in patients with advanced solid tumors and to assess preliminary safety and efficacy of which route of administration (intravenous or subcutaneous) will be selected for further development for the one expansion of patients, advanced non-small cell lung cancer (NSCLC) with defined genetic mutations.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
61
DRP-104 administered intravenously over 1 hour, three times per week (TIW) (Monday, Wednesday, Friday) for 2 consecutive weeks, one week off DRP-104 administered subcutaneously twice weekly (Monday/Thursday or Tuesday/Friday) every week OR thrice weekly (Monday, Wednesday, Friday) every week
atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks.
HonorHealth
Scottsdale, Arizona, United States
UCLA
Los Angeles, California, United States
AdventHealth Medical Group
Kissimmee, Florida, United States
Florida Cancer Specialist
Orlando, Florida, United States
Johns Hopkins Kimmel Institute
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
NYU Langone
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
...and 12 more locations
Maximum Tolerated Dose (MTD)
Safety
Time frame: anticipated 2 year
Pharmacokinetics (PK) of DRP-104
To assess and compare the concentration and partitioning of DRP-104 and the metabolites M1 and DON
Time frame: anticipated 1 year
Cmax of DRP-104
Area under the plasma concentration versus time curve (AUC)
Time frame: anticipated 1 year
Overall Response Rate (ORR)
Using RECIST criteria, determine the Overall Response Rate for DRP-104 subQ in NSCLC cohort 2 (months)
Time frame: anticipated 2 years
Disease Control Rate (DCR)
Disease Control Rate of all patient cohorts (months) for IV and SubQ administration
Time frame: anticipated 2 years
Progression-Free Survival (PFS)
Using RECIST criteria to assess the time for the disease to progress during treatment with DRP-104 (months)
Time frame: anticipated 2 years
Overall Survival (OS)
Defined as the time (months) from the start of treatment to death
Time frame: anticipated 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.