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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

Primary Purpose

Breast Cancer, Ovarian Cancer, Pancreas Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
TNG348
Olaparib
Sponsored by
Tango Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring BRCA mutant, HRD positive, solid tumors, USP1, TNG348

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Single Agent Dose Escalation

    Combination Dose Escalation

    Single agent dose expansion in breast cancer

    Single agent dose expansion in ovarian cancer

    Combination therapy dose expansion in breast cancer

    Combination therapy dose expansion in ovarian cancer

    Combination therapy dose expansion in pancreatic or prostate cancer

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

    Arm Description

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

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

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

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

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

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

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

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

    Outcomes

    Primary Outcome Measures

    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
    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

    Secondary Outcome Measures

    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
    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
    Characterize the plasma PK profile
    To determine the Cmax of TNG348
    Characterize the plasma PK profile
    To determine the Tmax
    Characterize the plasma PK profile
    To determine the AUC0-t and AUC0-∞ of TNG348
    Characterize the plasma PK profile
    To determine the half-life of TNG348
    Characterize olaparib concentrations when administered with TNG348
    To characterize the pre treatment and trough concentration levels of olaparib when administered in combination with TNG348
    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

    Full Information

    First Posted
    September 15, 2023
    Last Updated
    September 26, 2023
    Sponsor
    Tango Therapeutics, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06065059
    Brief Title
    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

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 2023 (Anticipated)
    Primary Completion Date
    December 2025 (Anticipated)
    Study Completion Date
    June 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tango Therapeutics, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Sequential Assignment
    Model Description
    Phase 1 Dose Escalation and Phase 2 Dose Expansion
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    140 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Single Agent Dose Escalation
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 to estimate the MTD
    Arm Title
    Combination Dose Escalation
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 in combination with olaparib to estimate the MTD
    Arm Title
    Single agent dose expansion in breast cancer
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant breast cancer will receive TNG348 at the identified RP2D
    Arm Title
    Single agent dose expansion in ovarian cancer
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 at the identified RP2D
    Arm Title
    Combination therapy dose expansion in breast cancer
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant breast cancer will receive TNG348 in combination with olaparib at the identified RP2D
    Arm Title
    Combination therapy dose expansion in ovarian cancer
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 in combination with olaparib at the identified RP2D
    Arm Title
    Combination therapy dose expansion in pancreatic or prostate cancer
    Arm Type
    Experimental
    Arm Description
    Participants with BRCA 1/2 mutant pancreatic or prostate cancer will receive TNG348 in combination with olaparib at the identified RP2D
    Arm Title
    Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors
    Arm Type
    Experimental
    Arm Description
    Participants with HRD+ advanced or metastatic solid tumors will receive TNG348 in combination with olaparib at the identified RP2D
    Intervention Type
    Drug
    Intervention Name(s)
    TNG348
    Intervention Description
    Ubiquitin Specific Peptidase 1 (USP1) inhibitor
    Intervention Type
    Drug
    Intervention Name(s)
    Olaparib
    Other Intervention Name(s)
    Lynparza
    Intervention Description
    PARP inhibitor
    Primary Outcome Measure Information:
    Title
    To determine dosing for TNG348 alone and in combination (Phase 1 only)
    Description
    • To determine the MTD, RP2D(s), and dosing schedule of TNG348 single agent and in combination with olaparib
    Time Frame
    21 days
    Title
    Measure anti-tumor activity using RECIST 1.1 (Phase 2 only)
    Description
    To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment
    Time Frame
    56 days
    Secondary Outcome Measure Information:
    Title
    Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)
    Description
    To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment
    Time Frame
    56 days
    Title
    Characterize the safety and tolerability profile
    Description
    Measure frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in safety laboratory tests
    Time Frame
    21 days
    Title
    Characterize the plasma PK profile
    Description
    To determine the Cmax of TNG348
    Time Frame
    16 days
    Title
    Characterize the plasma PK profile
    Description
    To determine the Tmax
    Time Frame
    16 days
    Title
    Characterize the plasma PK profile
    Description
    To determine the AUC0-t and AUC0-∞ of TNG348
    Time Frame
    16 days
    Title
    Characterize the plasma PK profile
    Description
    To determine the half-life of TNG348
    Time Frame
    16 days
    Title
    Characterize olaparib concentrations when administered with TNG348
    Description
    To characterize the pre treatment and trough concentration levels of olaparib when administered in combination with TNG348
    Time Frame
    16 days
    Title
    Assess changes in levels of ubPCNA in response to TNG348 as single agent or in combination
    Description
    Measure ubPCNA in tumor tissue and blood, on study treatment relative to pre-treatment
    Time Frame
    22 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Adam Crystal, MD, PHD
    Phone
    857-320-4899
    Email
    clinicaltrials@tangtox.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Adam Crystal, MD, PHD
    Organizational Affiliation
    Tango Therapeutics, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    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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