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

Sponsor

Tango Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05275478

Collaborator

(none)

170

Enrollment

Locations

Arms

41.3

Anticipated Duration (Months)

28.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

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 170 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 (excluding gliomas) 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, 5 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

Anticipated Enrollment :

170 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)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 TNG908 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Mar 23, 2022

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Sep 1, 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

Outcome Measures

Primary Outcome Measures

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 v1.1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Known allergies, hypersensitivity, or intolerance to TNG908 or its excipients
Uncontrolled intercurrent illness that will limit compliance with the study requirements
Active infection requiring systemic therapy
Diagnosis of malignant glioma
Currently participating in or has planned participation in a study of another investigational agent or device
Impairment of GI function or disease that may significantly alter the absorption of oral TNG908
Active prior or concurrent malignancy.
Central nervous system metastases associated with progressive neurological symptoms
Current active liver disease from any cause
Known to be HIV positive, unless all of the following criteria are met:
CD4+ count ≥300/μL
Undetectable viral load
Receiving highly active antiretroviral therapy
Clinically relevant cardiovascular disease
A female patient who is pregnant or lactating
Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions
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

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Sarah Cannon Tennessee Oncology	Nashville	Tennessee	United States	37203
4	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
5	NEXT Oncology	San Antonio	Texas	United States	78229
6	NEXT Oncology	Fairfax	Virginia	United States	22031