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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Mayo Clinic Scottsdale
  Scottsdale, Arizona, United States Recruiting
• Sarah Cannon Research Institute Denver
  Denver, Colorado, United States Recruiting
• Georgetown University Medical Center
  Washington D.C., District of Columbia, United States Recruiting
• Mayo Clinic Jacksonville
  Jacksonville, Florida, United States Recruiting
• Northwestern Memorial Hospital
  Chicago, Illinois, United States Recruiting
• University of Indiana
  Indianapolis, Indiana, United States Recruiting

Study contacts

• Study coordinator: Maxim Pimpkin, MD, PhD
• Email: clinicaltrials@tangotx.com
• Phone: 857-320-4899

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.