Study to Evaluate TNG348 Alone and With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or HRD+ Solid Tumors

Breast Cancer Clinical Trial

Official title:

Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG348 Single Agent and in Combination With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or Other HRD+ Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06065059
• Other study ID #: TNG348-C101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 8, 2023
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Tango Therapeutics, Inc.
• Contact: Tiffany Wang, MD
• Phone: 857-320-4899
• Email: clinicaltrials[@]tangtox.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this interventional clinical trial is to learn about TNG348, a ubiquitin specific peptidase 1 (USP1) inhibitor, alone and in combination with olaparib in patients with BRCA 1/2 mutant or HRD+ solid tumors. The main question[s] it aims to answer are: - to evaluate the safety and tolerability of single agent and combination therapy - to determine the recommended dose for Phase 2 of single agent and combination therapy - to determine the pharmacokinetics of TNG348 as a single agent and in combination therapy - to evaluate the initial antineoplastic activity as a single agent and in combination therapy Participants will receive study treatment until they experience an undesirable side effect, their disease progresses or until they withdraw consent.

Description:

This is a first-in-human Phase 1/2, open-label, multi-center, dose-escalation and expansion study designed to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose(s) (RP2D) and evaluate the safety, tolerability, and preliminary antitumor activity of TNG348 single agent and in combination with olaparib in participants with BRCA1/2 mutant or other HRD+ advanced or metastatic solid tumors. In Phase 1 (dose escalation), the single agent component will explore escalating oral doses of TNG348 administered alone and in combination with olaparib. Participants in Phase 2 (dose expansion) will be dosed at the RP2D(s) determined from Phase 1 based on safety and tolerability demonstrated, along with the available PK data and studied during Phase 1, as applicable. In the Phase 2 portion of the study, both single agent and combination therapy may be evaluated to assess an early signal of clinical benefit, as well as for confirmation of safety and tolerability.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Is =18 years of age at the time of signature of the main study ICF.
• Has ECOG performance status of 0 or 1.
• Has advanced or metastatic solid tumor with measurable disease based on RECIST v1.1.
• All participants must have documented BRCA 1/2 mutant or other HRD+ in solid tumor, which is identified through a validated sequencing test
• Adequate organ and bone marrow function per local labs
• Negative serum pregnancy test result at screening
• Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

• Known allergies, hypersensitivity, or intolerance to TNG348, olaparib or its excipients
• Uncontrolled intercurrent illness that will limit compliance with the study requirements
• 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 study drug
• Active prior or concurrent malignancy.
• Central nervous system metastases associated with progressive neurological symptoms
• Participant with MDS
• Clinically relevant cardiovascular disease
• Participant with known active or chronic infection
• A female patient who is pregnant or lactating

Related Conditions & MeSH terms

• BRCA-Mutated Ovarian Carcinoma
• BRCA1 Mutation
• Breast Cancer
• Breast Neoplasms
• Carcinoma
• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreas Cancer
• Pancreatic Neoplasms
• Prostate Cancer

Intervention

Drug:
• TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
• Olaparib
PARP inhibitor

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	HealthONE	Denver	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York University Langone Health	New York	New York
United States	Mid Florida Cancer Centers	Orange City	Florida
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tango Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine dosing for TNG348 alone and in combination (Phase 1 only)	• To determine the MTD, RP2D(s), and dosing schedule of TNG348 single agent and in combination with olaparib	21 days
Primary	Measure anti-tumor activity using RECIST 1.1 (Phase 2 only)	To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment	56 days
Secondary	Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)	To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment	56 days
Secondary	Characterize the safety and tolerability profile	Measure frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in safety laboratory tests	21 days
Secondary	Characterize the plasma PK profile	To determine the Cmax of TNG348	16 days
Secondary	Characterize the plasma PK profile	To determine the Tmax	16 days
Secondary	Characterize the plasma PK profile	To determine the AUC0-t and AUC0-8 of TNG348	16 days
Secondary	Characterize the plasma PK profile	To determine the half-life of TNG348	16 days
Secondary	Characterize olaparib concentrations when administered with TNG348	To characterize the pre treatment and trough concentration levels of olaparib when administered in combination with TNG348	16 days
Secondary	Assess changes in levels of ubPCNA in response to TNG348 as single agent or in combination	Measure ubPCNA in tumor tissue and blood, on study treatment relative to pre-treatment	22 days