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

NCT ID: NCT06922591

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

183 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-31

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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PDAC PDAC - Pancreatic Ductal Adenocarcinoma NSCLC RAS Mutation MTAP Deletion Lung Cancer Pancreatic Cancer Metastatic Thoracic Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation 1A

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

RMC-6236

Intervention Type DRUG

RAS(ON) multi-selective inhibitor

Dose escalation 1B

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

RMC-9805

Intervention Type DRUG

RAS(ON) G12D selective covalent inhibitor

Dose Expansion 2A

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

RMC-6236

Intervention Type DRUG

RAS(ON) multi-selective inhibitor

Dose Expansion 2B

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

RMC-9805

Intervention Type DRUG

RAS(ON) G12D selective covalent inhibitor

Experimental: Dose Escalation 1C

Escalating doses of TNG462 in combination with mFOLFIRINOX

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

mFOLFIRINOX

Intervention Type DRUG

Chemotherapy

Experimental: Dose Escalation 1D

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

gemcitabine/nab-paclitaxel

Intervention Type DRUG

Chemotherapy

Experimental: Dose Expansion 2C

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

mFOLFIRINOX

Intervention Type DRUG

Chemotherapy

Experimental: Dose Expansion 2D

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

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

MTA cooperative PRMT5 inhibitor

gemcitabine/nab-paclitaxel

Intervention Type DRUG

Chemotherapy

Interventions

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TNG462

MTA cooperative PRMT5 inhibitor

Intervention Type DRUG

RMC-9805

RAS(ON) G12D selective covalent inhibitor

Intervention Type DRUG

RMC-6236

RAS(ON) multi-selective inhibitor

Intervention Type DRUG

mFOLFIRINOX

Chemotherapy

Intervention Type DRUG

gemcitabine/nab-paclitaxel

Chemotherapy

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Revolution Medicines, Inc.

INDUSTRY

Sponsor Role collaborator

Tango Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maxim Pimpkin, MD, PhD

Role: STUDY_DIRECTOR

Tango Therapeutics, Inc.

Locations

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Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status RECRUITING

Sarah Cannon Research Institute Denver

Denver, Colorado, United States

Site Status RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

University of Indiana

Indianapolis, Indiana, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

NEXT Dallas

Irving, Texas, United States

Site Status RECRUITING

NEXT Oncology

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maxim Pimpkin, MD, PhD

Role: CONTACT

857-320-4899

Other Identifiers

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TNG462-C102

Identifier Type: -

Identifier Source: org_study_id

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