Clinical trial NCT05275478: Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Solid Tumor
Keywords: MTAP deletion
PRMT5
cholangiocarcinoma
NSCLC
mesothelioma
MPNST
Tango
Glioblastoma multiforme
pancreatic
GBM
sarcoma
Lead sponsor: Tango Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-11
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 6 arms (parallel)
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Phase 1:
timeFrame: 28 days
measure: Phase 2:
timeFrame: 16 weeks
Secondary outcomes:
measure: Phase 1:
timeFrame: 16 weeks
measure: Phase 1 and 2:
timeFrame: 28 days
measure: Phase 1 and 2:
timeFrame: 16 days
measure: Phase 1 and 2:
timeFrame: 16 days
measure: Phase 1 and 2:
timeFrame: 16 days
measure: Phase 1 and 2:
timeFrame: 16 days
measure: Phase 1 and 2:
timeFrame: 16 days
measure: Phase 1 and 2:
timeFrame: 16 days
measure: Phase 1 and 2:
timeFrame: 28 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Grand Junction
country: United States
facility: Grand Valley Oncology
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre Léon Bérard
city: Saint-Herblain
country: France
facility: EDOG Institut de Cancerologie de l'Ouest
city: Toulouse
country: France
facility: Institut Oncopole Claudius Regaud
city: Villejuif
country: France
facility: Institute Gustav Roussy
Study officials:
affiliation: Tango Therapeutics, Inc.
name: Maxim Pimkin, MD, PhD
role: STUDY_DIRECTOR
References: