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

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

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC; Lung Cancer; Thoracic Cancer; Pancreatic Cancer Metastatic; PDAC; PDAC - Pancreatic Ductal Adenocarcinoma; RAS Mutation; MTAP Deletion
• Intervention / Treatment: Drug: TNG462; Drug: RMC-6236; Drug: RMC-9805; Drug: mFOLFIRINOX; Drug: gemcitabine/nab-paclitaxel

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.

• Study Type: Interventional
• Enrollment (Estimated): 183
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Maxim Pimpkin, MD, PhD; Phone Number: 857-320-4899; Email: clinicaltrials@tangotx.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5452
      • Recruiting
      • Mayo Clinic Scottsdale
      • Principal Investigator: Mitesh Borad, MD
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute Denver
      • Principal Investigator: Gerald Falchook, MD, MS
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University Medical Center
      • Principal Investigator: Marcus Noel, MD
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Jacksonville
      • Principal Investigator: Hani Babiker, MD
  • Illinois
    • Chicago, Illinois, United States, 60611-2908
      • Recruiting
      • Northwestern Memorial Hospital
      • Principal Investigator: Chengwei Peng, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • University of Indiana
      • Principal Investigator: Anita Turk, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Health Care
      • Principal Investigator: Naomi Fei, MD, MS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Harshabad Singh, MD
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Kimberly Perez, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Recruiting
      • Mayo Clinic Cancer Center
      • Principal Investigator: Kaushal Parikh, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Recruiting
      • Nebraska Cancer Specialists
      • Principal Investigator: Joel Michalski, MD, PhD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Principal Investigator: Kristen Spencer, DO, MPH
    • New York, New York, United States, 11065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Eileen O'Reilly, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7305
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Principal Investigator: Shetal Patel, MD, PhD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Principal Investigator: Jordi Rodon Ahnert, MD
    • Irving, Texas, United States, 74039
      • Recruiting
      • NEXT Dallas
      • Principal Investigator: Siraj Sen, MD
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
      • Principal Investigator: Vaia Florou, MD, MS
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology
      • Principal Investigator: Alexander Spira, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation 1A; Escalating oral doses of TNG462 in combination with oral RMC-6236	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: RMC-6236; RAS(ON) multi-selective inhibitor
Experimental: Dose escalation 1B; Escalating oral doses of TNG462 in combination with oral RMC-9805	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: RMC-9805; RAS(ON) G12D selective covalent inhibitor
Experimental: Dose Expansion 2A; Expansion arm at the RDE(s) of oral TNG462 in combination with oral RMC-6236	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: RMC-6236; RAS(ON) multi-selective inhibitor
Experimental: Dose Expansion 2B; Expansion arm at the RDE(s) of oral TNG462 in combination with oralRMC-9805	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: RMC-9805; RAS(ON) G12D selective covalent inhibitor
Experimental: Experimental: Dose Escalation 1C; Escalating doses of TNG462 in combination with mFOLFIRINOX	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: mFOLFIRINOX; Chemotherapy
Experimental: Experimental: Dose Escalation 1D; Escalating doses of TNG462 in combination with gemcitabine/nab-paclitaxel	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: gemcitabine/nab-paclitaxel; Chemotherapy
Experimental: Experimental: Dose Expansion 2C; Expansion arm at the RDE(s) of TNG462 in combination with mFOLFIRINOX	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: mFOLFIRINOX; Chemotherapy
Experimental: Experimental: Dose Expansion 2D; Expansion arm at the RDE(s) of TNG462 in combination with gemcitabine/nab-paclitaxel	Drug: TNG462; MTA cooperative PRMT5 inhibitor; Drug: gemcitabine/nab-paclitaxel; Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2: Cmax of TNG462 and in Combination	To characterize the Cmax of TNG462 in combination with RMC-6236 or RMC-9805	21 days
Phase 1 and 2: Tmax of TNG462 and in Combination	To characterize the Tmax of TNG462 in combination with RMC-6236 or RMC-9805	21 days
Phase 1 and 2: AUC of TNG462 and in Combination	To characterize the AUC of TNG462 and in combination with RMC-6236 or RMC-9805	21 days
Phase 1 and 2 Adverse Event Profile	To determine the safety and tolerability of TNG462 in combination with RMC-6236 or RMC-9805	21 days
Phase 1: 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
Phase 1 and 2: Tmax of TNG462 and in Combination	To characterize the Tmax of TNG462 in combination with mFOLFIRINOX, or gemcitabine/nab-paclitaxel	28 days
Phase 1 and 2: Cmax of TNG462 and in Combination	To characterize the Cmax of TNG462 in combination with mFOLFIRINOX, or gemcitabine/nab-paclitaxel	28 days
Phase 1 and 2: AUC of TNG462 and in Combination	To characterize the AUC of TNG462 in combination with mFOLFIRINOX, or gemcitabine/nab-paclitaxel	28 days
Phase 1 and 2 Adverse Event Profile	To determine the safety and tolerability of TNG462 in combination with mFOLFIRINOX or gemcitabine nab-paclitaxel	28 days

Collaborators and Investigators

• Sponsor: Tango Therapeutics, Inc.
• Collaborators: Revolution Medicines, Inc.
• Investigators: Study Director: Maxim Pimpkin, MD, PhD, Tango Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 28, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Targeted therapy; Thoracic; PRMT5 inhibitor; RMC-6236; RAS G12D; Multi RAS; RMC-9805
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: TNG462-C102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No