NCT06922591

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
183

participants targeted

Target at P75+ for phase_1

Timeline
19mo left

Started May 2025

Typical duration for phase_1

Geographic Reach
1 country

18 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress37%
May 2025Dec 2027

First Submitted

Initial submission to the registry

March 28, 2025

Completed
13 days until next milestone

First Posted

Study publicly available on registry

April 10, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

May 31, 2025

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

April 22, 2026

Status Verified

April 1, 2026

Enrollment Period

2 years

First QC Date

March 28, 2025

Last Update Submit

April 17, 2026

Conditions

Keywords

PRMT5 inhibitorRAS G12DMulti RASRMC-9805RMC-6236ThoracicTargeted therapy

Outcome Measures

Primary Outcomes (3)

  • Phase 1: Maximum Tolerated Dose

    To determine the MTD and RD(s) of TNG462 in combination with RMC-6236 or RMC-9805

    21 days

  • Phase 1: Maximum Tolerated Dose

    To determine the MTD and RD(s) of TNG462 in combination with mFOLFIRINOX or gemcitabine/nab-paclitaxel

    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

    12 weeks

Secondary Outcomes (9)

  • Phase 1: Combination Anti-neoplastic Activity

    12 weeks

  • Phase 1 and 2: Tmax of TNG462 and in Combination

    21 days

  • Phase 1 and 2: Tmax of TNG462 and in Combination

    28 days

  • Phase 1 and 2: Cmax of TNG462 and in Combination

    21 days

  • Phase 1 and 2: Cmax of TNG462 and in Combination

    28 days

  • +4 more secondary outcomes

Study Arms (8)

Dose Escalation 1A

EXPERIMENTAL

Escalating oral doses of TNG462 in combination with oral RMC-6236

Drug: TNG462Drug: RMC-6236

Dose escalation 1B

EXPERIMENTAL

Escalating oral doses of TNG462 in combination with oral RMC-9805

Drug: TNG462Drug: RMC-9805

Dose Expansion 2A

EXPERIMENTAL

Expansion arm at the RDE(s) of oral TNG462 in combination with oral RMC-6236

Drug: TNG462Drug: RMC-6236

Dose Expansion 2B

EXPERIMENTAL

Expansion arm at the RDE(s) of oral TNG462 in combination with oralRMC-9805

Drug: TNG462Drug: RMC-9805

Experimental: Dose Escalation 1C

EXPERIMENTAL

Escalating doses of TNG462 in combination with mFOLFIRINOX

Drug: TNG462Drug: mFOLFIRINOX

Experimental: Dose Escalation 1D

EXPERIMENTAL

Escalating doses of TNG462 in combination with gemcitabine/nab-paclitaxel

Drug: TNG462Drug: gemcitabine/nab-paclitaxel

Experimental: Dose Expansion 2C

EXPERIMENTAL

Expansion arm at the RDE(s) of TNG462 in combination with mFOLFIRINOX

Drug: TNG462Drug: mFOLFIRINOX

Experimental: Dose Expansion 2D

EXPERIMENTAL

Expansion arm at the RDE(s) of TNG462 in combination with gemcitabine/nab-paclitaxel

Drug: TNG462Drug: gemcitabine/nab-paclitaxel

Interventions

TNG462DRUG

MTA cooperative PRMT5 inhibitor

Dose Escalation 1ADose Expansion 2ADose Expansion 2BDose escalation 1BExperimental: Dose Escalation 1CExperimental: Dose Escalation 1DExperimental: Dose Expansion 2CExperimental: Dose Expansion 2D

RAS(ON) G12D selective covalent inhibitor

Dose Expansion 2BDose escalation 1B

RAS(ON) multi-selective inhibitor

Dose Escalation 1ADose Expansion 2A

Chemotherapy

Experimental: Dose Escalation 1CExperimental: Dose Expansion 2C

Chemotherapy

Experimental: Dose Escalation 1DExperimental: Dose Expansion 2D

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Is ≥18 years of age at the time of signature of the main study ICF.
  • Has an ECOG PS of 0 or 1.
  • Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene
  • Arms A and B only: Has a tumor with a RAS mutation
  • Pathologically documented metastatic PDAC or locally advanced, recurrent or metastatic NSCLC
  • Has received prior standard therapy
  • Arms A and B only: Must not have received prior RAS-targeted therapy
  • Has evidence of measurable disease based on RECIST v1.1.
  • Adequate organ function
  • Must be able to swallow tablets.
  • Negative pregnancy test at screening
  • Written informed consent must be obtained according to local guidelines

You may not qualify if:

  • Has received prior treatment with a PRMT5 inhibitor, or MAT2A inhibitor
  • Arms A and B only: Prior enrollment in any phase 3 clinical trial of RMC-6236 or RMC-9805
  • 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
  • Has uncontrolled intercurrent illness that will limit compliance with the study requirements.
  • Has an active infection requiring systemic therapy.
  • Is currently participating in or has planned concurrent participation in a study of another investigational agent or device.
  • Has impairment of GI function or disease that may significantly alter the absorption of the oral medications
  • Has known or suspected active or untreated CNS metastases associated with progressive neurological symptoms
  • Has current active liver disease from any cause
  • Is known to be HIV positive, unless all the following criteria are met:
  • CD4+ count ≥300/µL.
  • Undetectable viral load.
  • Receiving highly active antiretroviral therapy
  • Has clinically relevant cardiovascular disease
  • History of or presence of active interstitial lung disease
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5452, United States

RECRUITING

Sarah Cannon Research Institute Denver

Denver, Colorado, 80218, United States

RECRUITING

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, 60611-2908, United States

RECRUITING

University of Indiana

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905-0001, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68124, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 11065, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Dallas

Irving, Texas, 74039, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

NEXT Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Maxim Pimpkin, MD, PhD

    Tango Therapeutics, Inc.

    STUDY DIRECTOR

Central Study Contacts

Maxim Pimpkin, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Dose escalation of TNG462 + RMC-9805, TNG462 + RMC-6236, TNG462 + mFOLFIRINOX and TNG462 + gemcitabine/nab-paclitaxel, followed by expansion of each combination in MTAP loss and RAS mutant PDAC and NSCLC
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2025

First Posted

April 10, 2025

Study Start

May 31, 2025

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

April 22, 2026

Record last verified: 2026-04

Locations