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

• ClinicalTrials.gov Identifier: NCT05275478
• Recruitment Status: Recruiting
• First Posted: March 11, 2022
• Last Update Posted: February 8, 2023
• Sponsor: Tango Therapeutics, Inc.
• Information provided by (Responsible Party): Tango Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Locally Advanced Solid Tumor	Drug: TNG908	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 192 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 6 arms (parallel)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG908 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors
• Actual Study Start Date: March 23, 2022
• Estimated Primary Completion Date: April 2025
• Estimated Study Completion Date: September 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in NSCLC; Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Mesothelioma; Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Cholangiocarcinoma; Participants with MTAP-deleted cholangiocarcinoma will receive TNG908 at the identified RP2D	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in MPNST; Participants with MTAP-deleted malignant peripheral nerve sheath tumor (MPNST) will receive TNG908 at the identified RP2D	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in solid tumors; Participants with MTAP-deleted solid tumors will receive TNG908 at the identified RP2D	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Glioblastoma; Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D	Drug: TNG908; TNG908, a selective PRMT5 inhibitor, will be administered orally

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Phase 1: [ Time Frame: 16 weeks ]
   To assess preliminary evidence of anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1or modified RANO criteria
2. Phase 1 and 2: [ Time Frame: 28 days ]
   To describe the safety and tolerability profile of TNG908 by frequency and severity of AEs
3. Phase 1 and 2: [ Time Frame: 16 days ]
   Area under the plasma concentration versus time curve (AUC)
4. Phase 1 and 2: [ Time Frame: 16 days ]
   Time to achieve maximal plasma concentration (Tmax)
5. Phase 1 and 2: [ Time Frame: 16 days ]
   Maximum observed plasma concentration (Cmax)
6. Phase 1 and 2: [ Time Frame: 16 days ]
   Terminal elimination half-life (t1/2)
7. Phase 1 and 2: [ Time Frame: 16 days ]
   Apparent total plasma clearance when dosed orally (CL/F)
8. Phase 1 and 2: [ Time Frame: 16 days ]
   Apparent volume of distribution when dosed orally (Vz/F)
9. Phase 1 and 2: [ Time Frame: 28 days ]
   SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG908

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Tango Clinical Trials; (857) 320-4899; clinicaltrials@tangotx.com

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator: Ibiayi Dagogo-Jack, MD

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Candace Haddox, MD

United States, Missouri

Washington University; Recruiting

Saint Louis, Missouri, United States, 63110

Principal Investigator: Angela Hirbe, MD, PhD

United States, Tennessee

Sarah Cannon Tennessee Oncology; Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator: David Spigel, MD

United States, Texas

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Jordi Rodon Ahnert, MD

NEXT Oncology; Recruiting

San Antonio, Texas, United States, 78229

Principal Investigator: Tony Tolcher, MD

United States, Virginia

NEXT Oncology; Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator: Alex Spira, MD

France

Centre Léon Bérard; Recruiting

Lyon, France, 69373

Principal Investigator: Philippe Cassier, MD

Institute Gustav Roussy; Recruiting

Villejuif, France, 94805

Principal Investigator: Capucine Baldini, MD

Sponsors and Collaborators

Tango Therapeutics, Inc.

Investigators

• Study Director: Ron Weitzman, MD; Tango Therapeutics, Inc.

More Information

• Responsible Party: Tango Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05275478
• Other Study ID Numbers: TNG908-C101
• First Posted: March 11, 2022
• Last Update Posted: February 8, 2023
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tango Therapeutics, Inc.:

MTAP deletion; PRMT5; cholangiocarcinoma; NSCLC; mesothelioma; MPNST; Tango; Glioblastoma multiforme; pancreatic; GBM

Additional relevant MeSH terms:

Neoplasms