Dysautonomia International

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

Purpose

Conditions

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

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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

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 Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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 Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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

Recruiting Locations

Mayo Clinic Scottsdale
Scottsdale 5313457, Arizona 5551752 85259-5452

Sarah Cannon Research Institute Denver
Denver 5419384, Colorado 5417618 80218

Mayo Clinic Jacksonville
Jacksonville 4160021, Florida 4155751 32224

University of Indiana
Indianapolis 4259418, Indiana 4921868 46202

Dana-Farber Cancer Institute
Boston 4930956, Massachusetts 6254926 02115

Mayo Clinic Cancer Center
Rochester 5043473, Minnesota 5037779 55905-0001

Nebraska Cancer Specialists
Omaha 5074472, Nebraska 5073708 68124

NYU Langone Health
New York 5128581, New York 5128638 10016

Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638 11065

University of Texas MD Anderson Cancer Center
Houston 4699066, Texas 4736286 77030

NEXT Dallas
Irving 4700168, Texas 4736286 74039

NEXT Oncology
Fairfax 4758023, Virginia 6254928 22031

More Details

Status: Recruiting
Sponsor: Tango Therapeutics, Inc.

Study Contact

Maxim Pimpkin, MD, PhD
857-320-4899
clinicaltrials@tangotx.com

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.