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

NCT06065059 | Terminated Phase 1 FDA Drug

• 1 other identifier: TNG348-C101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)

  56 days

• Characterize the safety and tolerability profile

  21 days

• Characterize the plasma PK profile

  16 days

• Characterize the plasma PK profile

  16 days

• Characterize the plasma PK profile

  16 days

Study Arms (8)

Single Agent Dose Escalation

EXPERIMENTAL

Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 to estimate the MTD

Drug: TNG348

Combination Dose Escalation

EXPERIMENTAL

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; Drug: Olaparib

Single agent dose expansion in breast cancer

EXPERIMENTAL

Participants with BRCA 1/2 mutant breast cancer will receive TNG348 at the identified RP2D

Drug: TNG348

Single agent dose expansion in ovarian cancer

EXPERIMENTAL

Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 at the identified RP2D

Drug: TNG348

Combination therapy dose expansion in breast cancer

EXPERIMENTAL

Participants with BRCA 1/2 mutant breast cancer will receive TNG348 in combination with olaparib at the identified RP2D

Drug: TNG348; Drug: Olaparib

Combination therapy dose expansion in ovarian cancer

EXPERIMENTAL

Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 in combination with olaparib at the identified RP2D

Drug: TNG348; Drug: Olaparib

Combination therapy dose expansion in pancreatic or prostate cancer

EXPERIMENTAL

Participants with BRCA 1/2 mutant pancreatic or prostate cancer will receive TNG348 in combination with olaparib at the identified RP2D

Drug: TNG348; Drug: Olaparib

Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors

EXPERIMENTAL

Participants with HRD+ advanced or metastatic solid tumors will receive TNG348 in combination with olaparib at the identified RP2D

Drug: TNG348; Drug: Olaparib

Interventions

TNG348 DRUG

Ubiquitin Specific Peptidase 1 (USP1) inhibitor

Combination Dose Escalation; Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors; Combination therapy dose expansion in breast cancer; Combination therapy dose expansion in ovarian cancer; Combination therapy dose expansion in pancreatic or prostate cancer; Single Agent Dose Escalation; Single agent dose expansion in breast cancer; Single agent dose expansion in ovarian cancer

Olaparib DRUG

PARP inhibitor

Also known as: Lynparza

Combination Dose Escalation; Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors; Combination therapy dose expansion in breast cancer; Combination therapy dose expansion in ovarian cancer; Combination therapy dose expansion in pancreatic or prostate cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tango Therapeutics, Inc.: lead

Study Sites (7)

HealthONE

Denver, Colorado, 80218, United States

Location

Mid Florida Cancer Centers

Orange City, Florida, 32763, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Adam Crystal, MD, PhD

  Tango Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 Dose Escalation and Phase 2 Dose Expansion

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: October 3, 2023
• Study Start: December 8, 2023
• Primary Completion: May 22, 2024
• Study Completion: May 22, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)