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

• ClinicalTrials.gov Identifier: NCT05732831
• Recruitment Status: Recruiting
• First Posted: February 17, 2023
• Last Update Posted: April 5, 2024
• 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, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 159 participants.

Condition or disease	Intervention/treatment	Phase
Locally Advanced Solid Tumor	Drug: TNG462	Phase 1; Phase 2

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 in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 5 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D of TNG462. 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: 159 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 5 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 TNG462 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors
• Actual Study Start Date: May 26, 2023
• Estimated Primary Completion Date: May 2026
• Estimated Study Completion Date: September 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 to estimate the MTD	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in NSCLC; Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D	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	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	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	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	Drug: TNG462; TNG462, a selective PRMT5 inhibitor, will be administered orally

Outcome Measures

Primary Outcome Measures :

1. Phase 1 Maximum Tolerated Dose [ Time Frame: 28 days ]
   To determine the maximum tolerated dose (MTD) of TNG462
2. Phase 1 Dosing Schedule [ Time Frame: 28 days ]
   To determine the dosing schedule of TNG462
3. Phase 2 Anti-neoplastic Activity [ Time Frame: 16 weeks ]
   To assess anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or mRECIST v1.1

Secondary Outcome Measures :

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

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
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
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

Contacts and Locations

Contacts

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

Locations

United States, California

Stanford University; Recruiting

Palo Alto, California, United States, 94304

Principal Investigator: Christopher Chen

United States, Florida

Sylvester Comprehensive Cancer Center; Recruiting

Miami, Florida, United States, 33136

Principal Investigator: Jose Lutzky, MD

United States, Massachusetts

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Candace Haddox, MD

United States, New York

New York University Langone Health; Recruiting

New York, New York, United States, 10016

Principal Investigator: Salman Punekar, MD

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

United States, Utah

Huntsman Cancer Institute, University of Utah; Recruiting

Salt Lake City, Utah, United States, 84112

Principal Investigator: Ignacio Garrido-Iaguna, MD, PhD

France

Centre Berard Leon; Recruiting

Lyon, France, 69373

Principal Investigator: Philippe Cassier, MD

Institute Gustav Roussy; Recruiting

Villejuif, France, 94805

Principal Investigator: Capucine Baldini, MD

Spain

Vall d'Hebron Barcelona Hospital; Recruiting

Barcelona, Catalonia, Spain

Principal Investigator: Irene Brana, MD

Hospital Universitario Fundacion Jimenez Diaz; Recruiting

Madrid, Spain, 28040

Principal Investigator: Victor Moreno Garcia, MD

Hospital de Sanchinarro; Recruiting

Madrid, Spain, 28050

Principal Investigator: Emiliano Calvo Aller, MD

Sponsors and Collaborators

Tango Therapeutics, Inc.

Investigators

• Study Director: Ellen Hooper, MD; Tango Therapeutics, Inc.

More Information

• Responsible Party: Tango Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05732831
• Other Study ID Numbers: TNG462-C101
• First Posted: February 17, 2023
• Last Update Posted: April 5, 2024
• Last Verified: April 2024

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; pancreatic; sarcoma

Additional relevant MeSH terms:

Neoplasms