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TNG462 combined with RAS inhibitors or chemotherapy for MTAP‑loss pancreatic and RAS‑mutant lung cancer

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

Phase1; Phase2 Interventional Tango Therapeutics, Inc. · NCT06922591

This trial will test whether taking oral TNG462 together with RAS inhibitors or standard chemotherapy is safe and helps people with MTAP‑loss pancreatic cancer or RAS‑mutant non‑small cell lung cancer.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment183 (estimated)
Ages18 Years and up
SexAll
SponsorTango Therapeutics, Inc. Industry-sponsored
Drugs / interventionschemotherapy
Locations18 sites (Scottsdale, Arizona and 17 other locations)
Trial IDNCT06922591 on ClinicalTrials.gov

What this trial studies

This is an open‑label, multicenter Phase 1/2 program consisting of a dose‑escalation part and dose‑expansion part to study oral TNG462 combined with RMC‑6236, RMC‑9805, mFOLFIRINOX, or gemcitabine/nab‑paclitaxel. The primary goals are to characterize safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of those combinations. RAS inhibitor arms enroll patients whose tumors have MTAP loss and a RAS mutation with metastatic PDAC or locally advanced/metastatic NSCLC, while the chemotherapy arms enroll MTAP‑loss locally advanced or metastatic PDAC. Once maximum tolerated dose (MTD) or recommended dose(s) are identified in escalation, individual expansion arms may open to further explore activity.

Who should consider this trial

Good fit: Adults (≥18) with metastatic or locally advanced PDAC or NSCLC, ECOG 0–1, measurable disease, adequate organ function, tumor MTAP loss (and a RAS mutation for the RAS inhibitor arms), and prior standard therapy are appropriate candidates.

Not a fit: Patients without tumor MTAP loss (or without a RAS mutation for the RAS arms), or those with prior exposure to PRMT5 or MAT2A inhibitors (or prior RAS‑targeted therapy for Arms A/B) are unlikely to benefit from these combinations.

Why it matters

Potential benefit: If successful, these combinations could provide a new targeted treatment option for patients with MTAP‑loss PDAC or RAS‑mutant NSCLC who have progressed after standard therapy.

How similar studies have performed: Related early‑phase work on RAS pathway inhibitors and PRMT5/MAT2A pathway targeting shows promising preclinical activity and preliminary clinical signals, but definitive clinical benefit has not yet been established.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Scottsdale, Arizona and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions PDACPDAC - Pancreatic Ductal AdenocarcinomaNSCLCRAS MutationMTAP DeletionLung CancerPancreatic Cancer MetastaticThoracic Cancer
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.