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

Locally Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05732831
• Other study ID #: TNG462-C101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 26, 2023
• Est. completion date: September 2026

Study information

• Verified date: May 2024
• Source: Tango Therapeutics, Inc.
• Contact: Tango Clinical Trials
• Phone: (857) 320-4899
• Email: clinicaltrials[@]tangotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 159
• Est. completion date: September 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally

Locations

Country	Name	City	State
France	Centre Berard Leon	Lyon
France	Institute Gustav Roussy	Villejuif
Spain	Vall d'Hebron Barcelona Hospital	Barcelona	Catalonia
Spain	Hospital de Sanchinarro	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Henry Ford Cancer Center	Detroit	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Sarah Cannon Tennessee Oncology	Nashville	Tennessee
United States	New York University Langone Health	New York	New York
United States	Stanford University	Palo Alto	California
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Tango Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Maximum Tolerated Dose	To determine the maximum tolerated dose (MTD) of TNG462	28 days
Primary	Phase 1 Dosing Schedule	To determine the dosing schedule of TNG462	28 days
Primary	Phase 2 Anti-neoplastic Activity	To assess anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or mRECIST v1.1	16 weeks
Secondary	Phase 1 Anti-neoplastic Activity	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	16 weeks
Secondary	Phase 1 and 2 Adverse Event Profile	To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs	28 days
Secondary	Phase 1 and 2 Concentration versus Time Curve	Measure the area under the plasma concentration versus time curve (AUC)	16 days
Secondary	Phase 1 and 2 Time to Achieve Maximal Plasma Concentration	Measure the time to achieve maximal plasma concentration (Tmax)	16 days
Secondary	Phase 1 and 2 Maximum Observed Plasma Concentration	Measure the maximum observed plasma concentration (Cmax)	16 days
Secondary	Phase 1 and 2 Terminal Elimination Half-life	Determine the terminal elimination half-life (t1/2)	16 days
Secondary	Phase 1 and 2 Total Plasma Clearance	Determine the apparent total plasma clearance when dosed orally (CL/F)	16 days
Secondary	Phase 1 and 2 Volume of Distribution	Determine the apparent volume of distribution when dosed orally (Vz/F)	16 days
Secondary	Phase 1 and 2 SDMA Levels	SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462	28 days