A Phase 1/2, Multicenter, Open-Label Study to Evaluate Safety, Tolerability & Antitumor Activity of TNG462 in Combination With Other Agents in Patients With Pancreatic Cancer With MTAP Loss and Pancreatic or Non-Small Cell Lung Cancer With MTAP Loss & RAS Mutation
Summary
TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel. The study comprises a dose escalation phase and a dose expansion phase.
Detailed description
TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel. For the RAS inhibitor arms, the study will be conducted in patients with MTAP loss and RAS mutant metastatic pancreatic adenocarcinoma (PDAC) or locally advanced or metastatic non-small cell lung cancer (NSCLC). For the chemotherapy specific arms, the study will be conducted in patients with MTAP loss locally advanced or metastatic PDAC. The entire study (all arms) will be conducted in 2 parts: Phase 1 (dose escalation) and Phase 2 (dose expansion). Individual Arms in the dose expansion phase may open once the MTD and/or RD(s) has been determined for the corresponding combination in the dose escalation phase of the study.
Arms & interventions
- DrugTNG462
MTA cooperative PRMT5 inhibitor
- DrugRMC-9805
RAS(ON) G12D selective covalent inhibitor
- DrugRMC-6236
RAS(ON) multi-selective inhibitor
- DrugmFOLFIRINOX
Chemotherapy
- Druggemcitabine/nab-paclitaxel
Chemotherapy
Outcome measures
Primary
Phase 1: Maximum Tolerated Dose
To determine the MTD and RD(s) of TNG462 in combination with RMC-6236 or RMC-9805
Time frame: 21 days
Phase 1: Maximum Tolerated Dose
To determine the MTD and RD(s) of TNG462 in combination with mFOLFIRINOX or gemcitabine/nab-paclitaxel
Time frame: 28 days
Phase 2: Combination Anti-neoplastic Activity
To assess preliminary evidence of antineoplastic activity of TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel using RECIST 1.1
Time frame: 12 weeks
Secondary
Phase 1: Combination Anti-neoplastic Activity
Time frame: 12 weeks
Phase 1 and 2: Tmax of TNG462 and in Combination
Time frame: 21 days
Phase 1 and 2: Tmax of TNG462 and in Combination
Time frame: 28 days
Phase 1 and 2: Cmax of TNG462 and in Combination
Time frame: 21 days
Phase 1 and 2: Cmax of TNG462 and in Combination
Time frame: 28 days
Phase 1 and 2: AUC of TNG462 and in Combination
Time frame: 21 days
Phase 1 and 2: AUC of TNG462 and in Combination
Time frame: 28 days
Phase 1 and 2 Adverse Event Profile
Time frame: 21 days
Phase 1 and 2 Adverse Event Profile
Time frame: 28 days
Eligibility criteria
Study locations (18)
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5452
Sarah Cannon Research Institute Denver
Denver, Colorado, 80218
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Northwestern Memorial Hospital
Chicago, Illinois, 60611-2908
University of Indiana
Indianapolis, Indiana, 46202
University of Iowa Health Care
Iowa City, Iowa, 52242
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905-0001
Nebraska Cancer Specialists
Omaha, Nebraska, 68124
NYU Langone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 11065
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7305
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Dallas
Irving, Texas, 74039
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
NEXT Oncology
Fairfax, Virginia, 22031