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

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ClinicalTrials.gov Identifier: NCT06065059
Recruitment Status : Terminated (Terminated due to safety)
First Posted : October 3, 2023
Last Update Posted : May 31, 2024
Sponsor:
Information provided by (Responsible Party):
Tango Therapeutics, Inc.

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.


Condition or disease Intervention/treatment Phase
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 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1 Dose Escalation and Phase 2 Dose Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 8, 2023
Actual Primary Completion Date : May 22, 2024
Actual Study Completion Date : May 22, 2024


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: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor

Drug: Olaparib
PARP inhibitor
Other Name: Lynparza

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: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor

Drug: Olaparib
PARP inhibitor
Other Name: Lynparza

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
Other Name: Lynparza

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: TNG348
Ubiquitin Specific Peptidase 1 (USP1) inhibitor

Drug: Olaparib
PARP inhibitor
Other Name: Lynparza

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
Other Name: Lynparza




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Characterize the plasma PK profile [ Time Frame: 16 days ]
    To determine the Cmax of TNG348

  4. Characterize the plasma PK profile [ Time Frame: 16 days ]
    To determine the Tmax

  5. Characterize the plasma PK profile [ Time Frame: 16 days ]
    To determine the AUC0-t and AUC0-∞ of TNG348

  6. Characterize the plasma PK profile [ Time Frame: 16 days ]
    To determine the half-life of TNG348

  7. 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

  8. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06065059


Locations
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United States, Colorado
HealthONE
Denver, Colorado, United States, 80218
United States, Florida
Mid Florida Cancer Centers
Orange City, Florida, United States, 32763
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
New York University Langone Health
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Tango Therapeutics, Inc.
Investigators
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Study Director: Tiffany Wang, MD Tango Therapeutics, Inc.
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Responsible Party: Tango Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT06065059    
Other Study ID Numbers: TNG348-C101
First Posted: October 3, 2023    Key Record Dates
Last Update Posted: May 31, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tango Therapeutics, Inc.:
BRCA mutant
HRD positive
solid tumors
USP1
TNG348
Additional relevant MeSH terms:
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Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Breast Neoplasms
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases
Urogenital Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders
Breast Diseases
Skin Diseases
Digestive System Neoplasms
Digestive System Diseases
Pancreatic Diseases
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action