Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors

Phase 1

Active, not recruiting

• Conditions: Locally Advanced Solid Tumor
• Interventions: Drug: TNG908

• Registration Number: NCT05275478
• Lead Sponsor: Tango Therapeutics, Inc.

Brief Summary

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, TNG908, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 192 participants.

Detailed Description

This is a Phase 1/2 multi-center, open label study in solid tumor patients (including glioblastoma) who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG908 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 of TNG908. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Study Timeline

• Study First Submitted: 2022-02-18
• Study First Submitted QC: 2022-03-01
• Study First Posted: 2022-03-11
• Study Start: 2022-03-23
• Status Verified: 2025-04
• Primary Completion: 2025-04
• Last Update Submitted: 2025-04-04
• Last Update Posted: 2025-04-06
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 192

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 or Karnofsky performance status score ≥70.
3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor or for GBM, have R/R disease.
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 TNG908 or its excipients

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 TNG908

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	TNG908	Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD
Dose Expansion in NSCLC	TNG908	Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D
Dose Expansion in Mesothelioma	TNG908	Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D
Dose Expansion in Sarcoma	TNG908	Participants with MTAP-deleted sarcoma (soft tissue and bone) will receive TNG908 at the identified RP2D
Dose Expansion in solid tumors	TNG908	Participants with other MTAP-deleted solid tumors will receive TNG908 at the identified RP2D
Dose Expansion in Glioblastoma	TNG908	Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D
Dose Expansion in Pancreatic Ductal Adenocarcinoma	TNG908	Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG908 at the identified RP2D

Primary Outcome Measures

Name	Time	Method
Phase 1:	28 days	To determine the MTD and dosing schedule of TNG908
Phase 2:	16 weeks	To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1 or modified RANO criteria

Secondary Outcome Measures

Name	Time	Method
Phase 1 and 2:	28 days	SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG908
Phase 1:	16 weeks	To assess preliminary evidence of anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1or modified RANO criteria

Trial Locations

Locations (20)

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Grand Valley Oncology; 🇺🇸 Grand Junction, Colorado, United States

Florida Cancer Specialists & Research Institute; 🇺🇸 Lake Mary, Florida, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Sarah Cannon Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

NEXT Oncology; 🇺🇸 Fairfax, Virginia, United States

Institut Bergonié; 🇫🇷 Bordeaux, France

Centre Léon Bérard; 🇫🇷 Lyon, France

EDOG Institut de Cancerologie de l'Ouest; 🇫🇷 Saint-Herblain, France

Institut Oncopole Claudius Regaud; 🇫🇷 Toulouse, France

Institute Gustav Roussy; 🇫🇷 Villejuif, France