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

August 12, 2024 updated by: Tango Therapeutics, Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • HealthONE
    • Florida
      • Orange City, Florida, United States, 32763
        • Mid Florida Cancer Centers
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • New York University Langone Health
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center

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.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

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
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
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: Olaparib
PARP inhibitor
Other Names:
  • Lynparza
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
Experimental: Single agent dose expansion in breast cancer
Participants with BRCA 1/2 mutant breast cancer will receive TNG348 at the identified RP2D
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
Experimental: Single agent dose expansion in ovarian cancer
Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 at the identified RP2D
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
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: Olaparib
PARP inhibitor
Other Names:
  • Lynparza
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) 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: Olaparib
PARP inhibitor
Other Names:
  • Lynparza
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) 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
Drug: Olaparib
PARP inhibitor
Other Names:
  • Lynparza
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
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: Olaparib
PARP inhibitor
Other Names:
  • Lynparza
Drug: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine dosing for TNG348 alone and in combination (Phase 1 only)
Time Frame: 21 days
• 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)
Time Frame: 56 days
To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment
56 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)
Time Frame: 56 days
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
Time Frame: 21 days
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
Time Frame: 16 days
To determine the Cmax of TNG348
16 days
Characterize the plasma PK profile
Time Frame: 16 days
To determine the Tmax
16 days
Characterize the plasma PK profile
Time Frame: 16 days
To determine the AUC0-t and AUC0-∞ of TNG348
16 days
Characterize the plasma PK profile
Time Frame: 16 days
To determine the half-life of TNG348
16 days
Characterize olaparib concentrations when administered with TNG348
Time Frame: 16 days
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
Time Frame: 22 days
Measure ubPCNA in tumor tissue and blood, on study treatment relative to pre-treatment
22 days

Collaborators and Investigators

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

Sponsor

Tango Therapeutics, Inc.

Investigators

  • Study Director: Adam Crystal, MD, PhD, Tango Therapeutics, Inc.

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 Major Dates

Study Start (Actual)

December 8, 2023

Primary Completion (Actual)

May 22, 2024

Study Completion (Actual)

May 22, 2024

Study Registration Dates

First Submitted

September 15, 2023

First Submitted That Met QC Criteria

September 26, 2023

First Posted (Actual)

October 3, 2023

Study Record Updates

Last Update Posted (Actual)

August 13, 2024

Last Update Submitted That Met QC Criteria

August 12, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TNG348-C101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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