Clinical trial NCT06065059: Study to Evaluate TNG348 Alone and With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or HRD+ Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Ovarian Cancer
Pancreas Cancer
Prostate Cancer
BRCA1 Mutation
BRCA-Mutated Ovarian Carcinoma
BRCA-Associated Breast Carcinoma
HRD Positive Advanced Ovarian Cancer
Keywords: BRCA mutant
HRD positive
solid tumors
USP1
TNG348
Lead sponsor: Tango Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-03
Enrollment: 7
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 and Phase 2 Dose Expansion
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine dosing for TNG348 alone and in combination (Phase 1 only)
timeFrame: 21 days
measure: Measure anti-tumor activity using RECIST 1.1 (Phase 2 only)
timeFrame: 56 days
Secondary outcomes:
measure: Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)
timeFrame: 56 days
measure: Characterize the safety and tolerability profile
timeFrame: 21 days
measure: Characterize the plasma PK profile
timeFrame: 16 days
measure: Characterize the plasma PK profile
timeFrame: 16 days
measure: Characterize the plasma PK profile
timeFrame: 16 days
measure: Characterize the plasma PK profile
timeFrame: 16 days
measure: Characterize olaparib concentrations when administered with TNG348
timeFrame: 16 days
measure: Assess changes in levels of ubPCNA in response to TNG348 as single agent or in combination
timeFrame: 22 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: HealthONE
state: Colorado
city: Orange City
country: United States
facility: Mid Florida Cancer Centers
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Tango Therapeutics, Inc.
name: Adam Crystal, MD, PhD
role: STUDY_DIRECTOR
References: