Breast CancerPhase 1/2NCT06065059
Study to Evaluate TNG348 Alone and With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or HRD+ Solid Tumors
A Phase 1/2 study testing TNG348 and Olaparib in people with Breast Cancer and Ovarian Cancer, run by Tango Therapeutics, Inc. at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Ovarian Cancer, Pancreas Cancer
- What is being tested?
- TNG348 and Olaparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 7 sitesUnited States
- Study dates
- 8 Dec 2023to 22 May 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Participant with MDS
- Clinically relevant cardiovascular disease
- Participant with known active or chronic infection
- A female patient who is pregnant or lactating
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
HealthONE
Denver, Colorado, 80218
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
New York University Langone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mid Florida Cancer Centers
Orange City, Florida, 32763
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
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
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:
Read more
- 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.
Read the 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.
- Conditions
- Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer, BRCA1 Mutation, BRCA-Mutated Ovarian Carcinoma
- Being tested
- TNG348, Olaparib
- Keywords
- BRCA mutant, HRD positive, solid tumors, USP1, TNG348
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNG348Drug
Ubiquitin Specific Peptidase 1 (USP1) inhibitor
OlaparibDrug
Also called Lynparza
PARP inhibitor
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: TNG348; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 56 days
Secondary outcomes (8)
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
Measured: 56 days
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
Measured: 21 days
Characterize the plasma PK profile
To determine the Cmax of TNG348
Measured: 16 days
Characterize the plasma PK profile
To determine the Tmax
Measured: 16 days
Characterize the plasma PK profile
To determine the AUC0-t and AUC0-∞ of TNG348
Measured: 16 days
Characterize the plasma PK profile
To determine the half-life of TNG348
Measured: 16 days
Characterize olaparib concentrations when administered with TNG348
To characterize the pre treatment and trough concentration levels of olaparib when administered in combination with TNG348
Measured: 16 days
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
Measured: 22 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2023
- Study start8 Dec 2023
- Primary completion22 May 2024
- Study completion22 May 2024
Why it stopped: Terminated due to safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase 1 Dose Escalation and Phase 2 Dose Expansion
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tango Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adam Crystal, MD, PhD, Study director, Tango Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06065059
- Sponsor's protocol ID
- TNG348-C101
- Status last verified
- Aug 2024
- First submitted
- 15 Sep 2023
- Last updated
- 13 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
da Costa AA, Somuncu O, Ravindranathan R, Mukkavalli S, Martignetti DB, Nguyen H, Jiao Y, Lamarre BP, Sadatrezaei G, Moreau L, Liu J, Iyer DR, Lazaro JB, Shapiro GI, Parmar K, D'Andrea AD. Single-Stranded DNA Gap Accumulation Is a Functional Biomarker for USP1 Inhibitor Sensitivity. Cancer Res. 2024 Oct 15;84(20):3435-3446. doi: 10.1158/0008-5472.CAN-23-4007.
PubMed 38885312
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06065059
- Acronym / sponsor ID
- TNG348-C101
- Conditions
- Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer, BRCA1 Mutation, BRCA-Mutated Ovarian Carcinoma
- Keywords
- BRCA mutant, HRD positive, solid tumors, USP1, TNG348
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to safety
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Tango Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Dec 2023 (actual)
- Primary completion
- 22 May 2024 (actual)
- Study completion
- 22 May 2024 (actual)
- First posted
- 3 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
- Model description
- Phase 1 Dose Escalation and Phase 2 Dose Expansion
| Arm | Type | Receives |
|---|---|---|
| Single Agent Dose Escalation | Experimental | Drug: TNG348Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 to estimate the MTD |
| Combination Dose Escalation | Experimental | Drug: TNG348, Drug: OlaparibParticipants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 in combination with olaparib to estimate the MTD |
| Single agent dose expansion in breast cancer | Experimental | Drug: TNG348Participants with BRCA 1/2 mutant breast cancer will receive TNG348 at the identified RP2D |
| Single agent dose expansion in ovarian cancer | Experimental | Drug: TNG348Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 at the identified RP2D |
| Combination therapy dose expansion in breast cancer | Experimental | Drug: TNG348, Drug: OlaparibParticipants with BRCA 1/2 mutant breast cancer will receive TNG348 in combination with olaparib at the identified RP2D |
| Combination therapy dose expansion in ovarian cancer | Experimental | Drug: TNG348, Drug: OlaparibParticipants with BRCA 1/2 mutant ovarian cancer will receive TNG348 in combination with olaparib at the identified RP2D |
| Combination therapy dose expansion in pancreatic or prostate cancer | Experimental | Drug: TNG348, Drug: OlaparibParticipants with BRCA 1/2 mutant pancreatic or prostate cancer will receive TNG348 in combination with olaparib at the identified RP2D |
| Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors | Experimental | Drug: TNG348, Drug: OlaparibParticipants with HRD+ advanced or metastatic solid tumors will receive TNG348 in combination with olaparib at the identified RP2D |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNG348Ubiquitin Specific Peptidase 1 (USP1) inhibitor | Drug | 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 |
| OlaparibAlso: LynparzaPARP inhibitor | Drug | 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 |
Primary outcome
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
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
8 secondary outcomes
Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)
Time frame: 56 days
Characterize the safety and tolerability profile
Time frame: 21 days
Characterize the plasma PK profile
Time frame: 16 days
Characterize the plasma PK profile
Time frame: 16 days
Characterize the plasma PK profile
Time frame: 16 days
Characterize the plasma PK profile
Time frame: 16 days
Characterize olaparib concentrations when administered with TNG348
Time frame: 16 days
Assess changes in levels of ubPCNA in response to TNG348 as single agent or in combination
Time frame: 22 days
Results and safety
The study was stopped early (reason given: Terminated due to safety). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Derived from this study: PubMed 38885312da Costa AA, Somuncu O, Ravindranathan R, Mukkavalli S, Martignetti DB, Nguyen H, Jiao Y, Lamarre BP, Sadatrezaei G, Moreau L, Liu J, Iyer DR, Lazaro JB, Shapiro GI, Parmar K, D'Andrea AD. Single-Stranded DNA Gap Accumulation Is a Functional Biomarker for USP1 Inhibitor Sensitivity. Cancer Res. 2024 Oct 15;84(20):3435-3446. doi: 10.1158/0008-5472.CAN-23-4007.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Crystal, MD, PhD study director
Tango Therapeutics, Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TNG348 and Olaparib in people with Breast Cancer and Ovarian Cancer, run by Tango Therapeutics, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated due to safety). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine dosing for TNG348 alone and in combination (Phase 1 only) (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06065059, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2024.