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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT06922591Sponsor: Tango Therapeutics, Inc.Last updated: 2026-05-14

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1. Is ≥18 years of age at the time of signature of the main study ICF. 2. Has an ECOG PS of 0 or 1. 3. Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene 4. Arms A and B only: Has a tumor with a RAS mutation 5. Pathologically documented metastatic PDAC or locally advanced, recurrent or metastatic NSCLC 6. Has received prior standard therapy 7. Arms A and B only: Must not have received prior RAS-targeted therapy 8. Has evidence of measurable disease based on RECIST v1.1. 9. Adequate organ function 10. Must be able to swallow tablets. 11. Negative pregnancy test at screening 12. Written informed consent must be obtained according to local guidelines Exclusion Criteria: 1. Has received prior treatment with a PRMT5 inhibitor, or MAT2A inhibitor 2. Arms A and B only: Prior enrollment in any phase 3 clinical trial of RMC-6236 or RMC-9805 3. Known allergy, hypersensitivity or intolerance to TNG462 (all arms), RMC-6236 Arm A), RMC-9805 (Arm B), mFOLFIRINOX (Arm C), gemcitabine/nab-paclitaxel (Arm D) or their excipients 4. Has uncontrolled intercurrent illness that will limit compliance with the study requirements. 5. Has an active infection requiring systemic therapy. 6. Is currently participating in or has planned concurrent participation in a study of another investigational agent or device. 7. Has impairment of GI function or disease that may significantly alter the absorption of the oral medications 8. Has known or suspected active or untreated CNS metastases associated with progressive neurological symptoms 9. Has current active liver disease from any cause 10. Is known to be HIV positive, unless all the following criteria are met: 1. CD4+ count ≥300/µL. 2. Undetectable viral load. 3. Receiving highly active antiretroviral therapy 11. Has clinically relevant cardiovascular disease 12. History of or presence of active interstitial lung disease 13. Is a female patient who is pregnant or lactating 14. Is unwilling or unable to comply with the scheduled visits, study treatment administration plan, laboratory tests or other study procedures and study restrictions. 15. Has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion may affect the safety of the patient or impair the ability to assess study results

Study locations (18)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5452

Recruiting
Mitesh Borad, MD · Principal Investigator

Sarah Cannon Research Institute Denver

Denver, Colorado, 80218

Recruiting
Gerald Falchook, MD, MS · Principal Investigator

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007

Recruiting
Marcus Noel, MD · Principal Investigator

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224

Recruiting
Hani Babiker, MD · Principal Investigator

Northwestern Memorial Hospital

Chicago, Illinois, 60611-2908

Recruiting
Chengwei Peng, MD · Principal Investigator

University of Indiana

Indianapolis, Indiana, 46202

Recruiting
Anita Turk, MD · Principal Investigator

University of Iowa Health Care

Iowa City, Iowa, 52242

Recruiting
Naomi Fei, MD, MS · Principal Investigator

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Harshabad Singh, MD · Principal Investigator

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115

Recruiting
Kimberly Perez, MD · Principal Investigator

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905-0001

Recruiting
Kaushal Parikh, MD · Principal Investigator

Nebraska Cancer Specialists

Omaha, Nebraska, 68124

Recruiting
Joel Michalski, MD, PhD · Principal Investigator

NYU Langone Health

New York, New York, 10016

Recruiting
Kristen Spencer, DO, MPH · Principal Investigator

Memorial Sloan Kettering Cancer Center

New York, New York, 11065

Recruiting
Eileen O'Reilly, MD · Principal Investigator

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7305

Recruiting
Shetal Patel, MD, PhD · Principal Investigator

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Jordi Rodon Ahnert, MD · Principal Investigator

NEXT Dallas

Irving, Texas, 74039

Recruiting
Siraj Sen, MD · Principal Investigator

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112

Recruiting
Vaia Florou, MD, MS · Principal Investigator

NEXT Oncology

Fairfax, Virginia, 22031

Recruiting
Alexander Spira, MD, PhD · Principal Investigator
Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients | Cancerify