Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 as a Single Agent and in Combination in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors

This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 225 participants.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Solid Tumor
• Intervention / Treatment: Drug: TNG462; Drug: Pembrolizumab

Detailed Description

This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG462 administered as a single agent and in combination with pembrolizumab in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 6 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D(s) of TNG462 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• France
  • Brest, France, 29200
    • Recruiting
    • CHU de Brest
    • Principal Investigator: Jean-Philippe Metges, MD
  • Lyon, France, 69373
    • Recruiting
    • Centre Berard Leon
    • Principal Investigator: Philippe CASSIER, MD
  • Saint-Herblain, France, 44805
    • Recruiting
    • Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS
    • Principal Investigator: Ludovic Doucet, MD, MSc
  • Villejuif, France, 94805
    • Recruiting
    • Institute Gustav Roussy
    • Principal Investigator: Kaissa Ouali, MD
• Spain
  • Barcelona, Spain, 08908
    • Recruiting
    • ICO L'Hospitalet - Hospital Duran i Reynals
    • Principal Investigator: Mariona Calvo Campos, MD
  • Barcelona, Spain, 08023
    • Recruiting
    • Hospital HM Nou Delfos
    • Principal Investigator: Tatiana Hernandez Guerrero, MD
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundación Jimenez Díaz
    • Principal Investigator: Victor Moreno Garcia, MD
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital de Sanchinarro
    • Principal Investigator: Emiliano Calvo Aller, MD
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
    • Principal Investigator: Javier Garcia-Corbacho, MD
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Principal Investigator: Alejandro Falcon, MD
  • Catalonia
    • Barcelona, Catalonia, Spain
      • Recruiting
      • Vall d'Hebron Barcelona Hospital
      • Principal Investigator: Irene Brana, MD
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Principal Investigator: Christopher Chen
  • Colorado
    • Grand Junction, Colorado, United States, 81505
      • Recruiting
      • Grand Valley Oncology
      • Principal Investigator: Jonathan King, MD
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Completed
      • Florida Cancer Specialists & Research Institute
    • Miami, Florida, United States, 33136
      • Recruiting
      • Sylvester Comprehensive Cancer Center
      • Principal Investigator: Jose Lutzky, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University Chicago Medicine
      • Principal Investigator: Hedy Kindler, MD
    • Urbana, Illinois, United States, 61801
      • Recruiting
      • Carle Cancer Center
      • Principal Investigator: Tammay Sahai, MD
    • Zion, Illinois, United States, 60099
      • Recruiting
      • Midwestern Regional Medical Center, City of Hope Chicago
      • Principal Investigator: Evan Pisick, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Candace Haddox, MD
    • Boston, Massachusetts, United States, 02214
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Ibiayi Dagogo-Jack, MD
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Cancer Center
      • Principal Investigator: Amy Weise, DO
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Health
      • Principal Investigator: Salman Punekar, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Tennessee Oncology
      • Principal Investigator: David Spigel, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Principal Investigator: Jordi Rodon Ahnert, 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 Virginia
      • Principal Investigator: Alexander Spira, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: ≥18 years-of-age at the time of signature of the main study ICF
2. Performance status: ECOG Performance Score of 0 to 1
3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor
4. Prior standard therapy, as available
5. Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by next- generation sequencing or absence of MTAP protein in a tumor detected by IHC.
6. Adequate organ function/reserve per local labs
7. Adequate liver function per local labs
8. Adequate renal function per local labs
9. Negative serum pregnancy test result at screening
10. Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

1. Known allergies, hypersensitivity, or intolerance to TNG462, or its excipients or to pembrolizumab in the combination treatment arms
2. Uncontrolled intercurrent illness that will limit compliance with the study requirements
3. Active infection requiring systemic therapy
4. Currently participating in or has planned participation in a study of another investigational agent or device
5. Impairment of GI function or disease that may significantly alter the absorption of oral TNG462
6. Active prior or concurrent malignancy.
7. Central nervous system metastases associated with progressive neurological symptoms
8. Current active liver disease from any cause

9. Known to be HIV positive, unless all of the following criteria are met:

   1. CD4+ count ≥300/μL
   2. Undetectable viral load
   3. Receiving highly active antiretroviral therapy
10. Clinically relevant cardiovascular disease
11. A female patient who is pregnant or lactating
12. Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions
13. Patient 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 assessment of 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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 single agent and in combination with pembrolizumab to estimate the MTD	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally; Drug: Pembrolizumab; An anti PD-1 antibody, will be administered intravenously; Other Names: Keytruda
Experimental: Dose Expansion in NSCLC; Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Mesothelioma; Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Pancreatic Ductal Adenocarcinoma; Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Sarcoma; Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Solid Tumors; Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in NSCLC in Combination with Pembrolizumab; Participants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally; Drug: Pembrolizumab; An anti PD-1 antibody, will be administered intravenously; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Dosing Schedule	To determine the dosing schedule of TNG462	28 days
Phase 1 Maximum Tolerated Dose	To determine the maximum tolerated dose (MTD) of TNG462 when administered as a single agent and in combination with pembrolizumab	28 days and 21 days
Phase 2 Anti-neoplastic Activity	To assess anti-neoplastic activity of TNG462 administered single agent and in combination with pembrolizumab in patients with MTAP-deleted advanced solid tumors by RECIST v1.1, iRECIST or mRECIST v1.1	16 weeks and 18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2 Concentration versus Time Curve	Measure the area under the plasma concentration versus time curve (AUC)	16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration	Measure the time to achieve maximal plasma concentration (Tmax)	16 days
Phase 1 and 2 Maximum Observed Plasma Concentration	Measure the maximum observed plasma concentration (Cmax)	16 days
Phase 1 and 2 Terminal Elimination Half-life	Determine the terminal elimination half-life (t1/2)	16 days
Phase 1 and 2 Total Plasma Clearance	Determine the apparent total plasma clearance when dosed orally (CL/F)	16 days
Phase 1 and 2 Volume of Distribution	Determine the apparent volume of distribution when dosed orally (Vz/F)	16 days
Phase 1 and 2 SDMA Levels	SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462	28 days
Phase 1 Anti-neoplastic Activity	To assess preliminary evidence of anti-neoplastic activity of TNG462 as a single agent and when administered in combination with pembrolizumab in patients with MTAP-deleted advanced solid tumors by RECIST v1.1, iRECIST or mRECIST v1.1	16 weeks
Phase 1 and 2 Adverse Event Profile	To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs	28 days and 21 days

Collaborators and Investigators

• Sponsor: Tango Therapeutics, Inc.
• Investigators: Study Director: Maxim Pimpkin, MD, Tango Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: renal; NSCLC; mesothelioma; breast; cholangiocarcinoma; liver; pancreatic; MPNST; sarcoma; gallbladder; Tango; PRMT5; MTAP deletion; urothelial
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Adenoma; Neoplasms, Mesothelial; Carcinoma; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neurofibroma; Fibrosarcoma; Neoplasms, Fibrous Tissue; Mesothelioma; Cholangiocarcinoma; Sarcoma; Neurofibrosarcoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: TNG462-C101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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