Study To Evaluate TNG348 Alone And With A PARP Inhibitor In Patients With BRCA 1/2 Mutant Or HRD+ Solid Tumors

Study Overview

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

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.

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.

Breast Cancer
Ovarian Cancer
Pancreas Cancer
Prostate Cancer
BRCA1 Mutation
BRCA-Mutated Ovarian Carcinoma
BRCA-Associated Breast Carcinoma
HRD Positive Advanced Ovarian Cancer

DRUG: TNG348
DRUG: Olaparib

TNG348-C101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-09-15	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-08-12
First Submitted that Met QC Criteria 2023-09-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-08-13
First Posted (ACTUAL) 2023-10-03	Results First Posted N/A	Last Verified 2024-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Single Agent Dose Escalation Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 to estimate the MTD
EXPERIMENTAL: Combination Dose Escalation Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 in combination with olaparib to estimate the MTD	DRUG: TNG348 Ubiquitin Specific Peptidase 1 (USP1) inhibitor DRUG: Olaparib PARP inhibitor
EXPERIMENTAL: Single agent dose expansion in breast cancer Participants with BRCA 1/2 mutant breast cancer will receive TNG348 at the identified RP2D
EXPERIMENTAL: Single agent dose expansion in ovarian cancer Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 at the identified RP2D
EXPERIMENTAL: Combination therapy dose expansion in breast cancer Participants with BRCA 1/2 mutant breast cancer will receive TNG348 in combination with olaparib at the identified RP2D	DRUG: TNG348 Ubiquitin Specific Peptidase 1 (USP1) inhibitor DRUG: Olaparib PARP inhibitor
EXPERIMENTAL: Combination therapy dose expansion in ovarian cancer Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 in combination with olaparib at the identified RP2D	DRUG: TNG348 Ubiquitin Specific Peptidase 1 (USP1) inhibitor DRUG: Olaparib PARP inhibitor
EXPERIMENTAL: Combination therapy dose expansion in pancreatic or prostate cancer Participants with BRCA 1/2 mutant pancreatic or prostate cancer will receive TNG348 in combination with olaparib at the identified RP2D
EXPERIMENTAL: Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors Participants with HRD+ advanced or metastatic solid tumors will receive TNG348 in combination with olaparib at the identified RP2D	DRUG: TNG348 Ubiquitin Specific Peptidase 1 (USP1) inhibitor DRUG: Olaparib PARP inhibitor

Primary Outcome Measures	Measure Description	Time Frame
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
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 Outcome Measures	Measure Description	Time Frame
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
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
Characterize the plasma PK profile	To determine the Cmax of TNG348	16 days
Characterize the plasma PK profile	To determine the Tmax	16 days
Characterize the plasma PK profile	To determine the AUC0-t and AUC0-∞ of TNG348	16 days
Characterize the plasma PK profile	To determine the half-life of TNG348	16 days
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
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Adam Crystal, MD, PhD, Tango Therapeutics, Inc.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record