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NCT06922591PHASE1, PHASE2Recruiting

Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients

Tango Therapeutics, Inc.

Start Date

5/31/2025

Completion Date

12/1/2027

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

TNG462

DRUG

RMC-9805

DRUG

RMC-6236

DRUG

mFOLFIRINOX

DRUG

gemcitabine/nab-paclitaxel

Interested in This Trial?

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Conditions

PDACPDAC - Pancreatic Ductal AdenocarcinomaNSCLCRAS MutationMTAP DeletionLung CancerPancreatic Cancer MetastaticThoracic Cancer

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona 85259-5452

United States

Sarah Cannon Research Institute Denver

Denver, Colorado 80218

United States

Georgetown University Medical Center

Washington D.C., District of Columbia 20007

United States

Mayo Clinic Jacksonville

Jacksonville, Florida 32224

United States

Northwestern Memorial Hospital

Chicago, Illinois 60611-2908

United States

University of Indiana

Indianapolis, Indiana 46202

United States

University of Iowa Health Care

Iowa City, Iowa 52242

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02115

United States

Mayo Clinic Cancer Center

Rochester, Minnesota 55905-0001

United States

Nebraska Cancer Specialists

Omaha, Nebraska 68124

United States

NYU Langone Health

New York, New York 10016

United States

Memorial Sloan Kettering Cancer Center

New York, New York 11065

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599-7305

United States

University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

NEXT Dallas

Irving, Texas 74039

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

NEXT Oncology

Fairfax, Virginia 22031

United States