Study to see how safe is TNG908 at different doses in patients with solid tumors that have a gene called MTAP missing

Phase 1/2

Active, not recruiting

• Conditions: "Ph1: •Locally advanced (LA) or metastatic MTAP-deleted (met.MTAP-del.) solid tumors •MTAP-del.relapsed or refrac. Grade 4 astrocytoma or glioblastoma multiforme (R/R GBM) Ph2: A1:LA or met.MTAP-del. squamous and nonsquamous NSCLC A2:LA or met.MTAP-del. mesothelioma A3:LA or met.MTAP-del. sarcoma A4:LA or met.MTAP-del. pancreatic ductal adenocarcinoma or adenosquamous carcinoma w/predominantly adenocarcinoma histology A5:Other LA or met.MTAP-del. solid tumors A6:MTAP-del. R/R GBM"

• Registration Number: 2024-511976-34-00
• Lead Sponsor: Tango Therapeutics Inc.

Brief Summary

"Phase 1: To determine the MTD and RP2D(s) of TNG908

Phase 2: To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors"

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: 2025-07
• Last Update Submitted: 2025-07-22
• Last Update Posted: 2025-07-23
• Primary Completion: 2025-12
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

"_Age: ≥18 years-of-age at the time of signature of the main study ICF _Performance status: a)Patients with solid tumors other than R/R GBM: ECOG performance status score of 0 to 1 b) Patients with R/R GBM: Karnofsky performance status score ≥70 _For solid tumors other than R/R GBM, have confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor or for GBM, have R/R GBM _Prior standard therapy, as available _Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by a validated NGS test, or absence of MTAP protein in a tumor detected by a validated IHC test. _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

Not have received prior treatment with a PRMT5 inhibitor.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase 1: Incidence of DLTs within the first 28 days of treatment with TNG908 monotherapy Phase 2: - ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment - DOR as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment		Phase 1: Incidence of DLTs within the first 28 days of treatment with TNG908 monotherapy Phase 2: - ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment - DOR as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment
- PFS by investigator assessment - CBR (CR + PR + stable disease) at 16 weeks		- PFS by investigator assessment - CBR (CR + PR + stable disease) at 16 weeks

Secondary Outcome Measures

Name	Time	Method
"Secondary – Phases 1 and 2 - Type, frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in vital signs, ECGs, ECOG performance status or Karnofsky performance status, and safety laboratory tests - PK parameters of TNG908 including, but not limited to, Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, λz, CL/F, Vz/F, Rac for Cmax and AUC, and Ctrough - Changes in SDMA levels in tumor after dosing with TNG908 "		"Secondary – Phases 1 and 2 - Type, frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in vital signs, ECGs, ECOG performance status or Karnofsky performance status, and safety laboratory tests - PK parameters of TNG908 including, but not limited to, Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, λz, CL/F, Vz/F, Rac for Cmax and AUC, and Ctrough - Changes in SDMA levels in tumor after dosing with TNG908 "

Trial Locations

Locations (5)

Centre Leon Berard; 🇫🇷 Lyon, France

Institut De Cancerologie De L Ouest; 🇫🇷 Saint-Herblain Cedex, France

Oncopole Claudius Regaud; 🇫🇷 Toulouse Cedex 9, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Centre Leon Berard

🇫🇷Lyon, France

Philippe CASSIER

Site contact

+33426556833

philippe.cassier@lyon.unicancer.fr