Clinical trial NCT05732831: Safety and Tolerability of TNG462 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 TNG462 as a Single Agent and in Combination in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Solid Tumor
Keywords: MTAP deletion
PRMT5
cholangiocarcinoma
NSCLC
mesothelioma
MPNST
Tango
pancreatic
sarcoma
urothelial
gallbladder
liver
renal
breast
Lead sponsor: Tango Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-17
Enrollment: 225
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 5 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, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 225 participants.

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 administered as a single agent and in combination with pembrolizumab 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(s) of TNG462 and in combination. 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
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 or to pembrolizumab in the combination treatment arms
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

Primary outcomes:
measure: Phase 1 Maximum Tolerated Dose
timeFrame: 28 days and 21 days
measure: Phase 1 Dosing Schedule
timeFrame: 28 days
measure: Phase 2 Anti-neoplastic Activity
timeFrame: 16 weeks and 18 weeks
Secondary outcomes:
measure: Phase 1 Anti-neoplastic Activity
timeFrame: 16 weeks
measure: Phase 1 and 2 Adverse Event Profile
timeFrame: 28 days and 21 days
measure: Phase 1 and 2 Concentration versus Time Curve
timeFrame: 16 days
measure: Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
timeFrame: 16 days
measure: Phase 1 and 2 Maximum Observed Plasma Concentration
timeFrame: 16 days
measure: Phase 1 and 2 Terminal Elimination Half-life
timeFrame: 16 days
measure: Phase 1 and 2 Total Plasma Clearance
timeFrame: 16 days
measure: Phase 1 and 2 Volume of Distribution
timeFrame: 16 days
measure: Phase 1 and 2 SDMA Levels
timeFrame: 28 days
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Grand Junction
country: United States
facility: Grand Valley Oncology
state: Colorado
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: University Chicago Medicine
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center, City of Hope Chicago
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: Detroit
country: United States
facility: Henry Ford Cancer Center
state: Michigan
city: New York
country: United States
facility: New York University Langone Health
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: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Fairfax
country: United States
facility: Next Oncology Virginia
state: Virginia
city: Brest
country: France
facility: CHU de Brest
city: Lyon
country: France
facility: Centre Berard Leon
city: Saint-Herblain
country: France
facility: Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS
city: Villejuif
country: France
facility: Institute Gustav Roussy
city: Barcelona
country: Spain
facility: Vall d'Hebron Barcelona Hospital
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital de Sanchinarro
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Tango Therapeutics, Inc.
name: Maeve Waldron-Lynch, MD
role: STUDY_DIRECTOR
References: