Ignite Creation Date:
2025-12-24 @ 2:55 PM
Ignite Modification Date:
2025-12-26 @ 3:45 PM
Study NCT ID:
NCT06065059
Status:
TERMINATED
Last Update Posted:
2024-08-13
First Post:
2023-09-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study to Evaluate TNG348 Alone and With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or HRD+ Solid Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D010051', 'term': 'Ovarian Neoplasms'}, {'id': 'D010190', 'term': 'Pancreatic Neoplasms'}, {'id': 'D011471', 'term': 'Prostatic Neoplasms'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D004701', 'term': 'Endocrine Gland Neoplasms'}, {'id': 'D010049', 'term': 'Ovarian Diseases'}, {'id': 'D000291', 'term': 'Adnexal Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D005833', 'term': 'Genital Neoplasms, Female'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D005834', 'term': 'Genital Neoplasms, Male'}, {'id': 'D005832', 'term': 'Genital Diseases, Male'}, {'id': 'D011469', 'term': 'Prostatic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C531550', 'term': 'olaparib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Phase 1 Dose Escalation and Phase 2 Dose Expansion'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 7}}, 'statusModule': {'whyStopped': 'Terminated due to safety', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2023-12-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2024-05-22', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-08-12', 'studyFirstSubmitDate': '2023-09-15', 'studyFirstSubmitQcDate': '2023-09-26', 'lastUpdatePostDateStruct': {'date': '2024-08-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-10-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-05-22', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To determine dosing for TNG348 alone and in combination (Phase 1 only)', 'timeFrame': '21 days', 'description': '• To determine the MTD, RP2D(s), and dosing schedule of TNG348 single agent and in combination with olaparib'}, {'measure': 'Measure anti-tumor activity using RECIST 1.1 (Phase 2 only)', 'timeFrame': '56 days', 'description': 'To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment'}], 'secondaryOutcomes': [{'measure': 'Measure anti-tumor activity using RECIST 1.1 (Phase 1 only)', 'timeFrame': '56 days', 'description': 'To assess the antitumor activity of TNG348 single agent and in combination using RECIST 1.1 per investigator assessment'}, {'measure': 'Characterize the safety and tolerability profile', 'timeFrame': '21 days', 'description': 'Measure frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in safety laboratory tests'}, {'measure': 'Characterize the plasma PK profile', 'timeFrame': '16 days', 'description': 'To determine the Cmax of TNG348'}, {'measure': 'Characterize the plasma PK profile', 'timeFrame': '16 days', 'description': 'To determine the Tmax'}, {'measure': 'Characterize the plasma PK profile', 'timeFrame': '16 days', 'description': 'To determine the AUC0-t and AUC0-∞ of TNG348'}, {'measure': 'Characterize the plasma PK profile', 'timeFrame': '16 days', 'description': 'To determine the half-life of TNG348'}, {'measure': 'Characterize olaparib concentrations when administered with TNG348', 'timeFrame': '16 days', 'description': 'To characterize the pre treatment and trough concentration levels of olaparib when administered in combination with TNG348'}, {'measure': 'Assess changes in levels of ubPCNA in response to TNG348 as single agent or in combination', 'timeFrame': '22 days', 'description': 'Measure ubPCNA in tumor tissue and blood, on study treatment relative to pre-treatment'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['BRCA mutant', 'HRD positive', 'solid tumors', 'USP1', 'TNG348'], 'conditions': ['Breast Cancer', 'Ovarian Cancer', 'Pancreas Cancer', 'Prostate Cancer', 'BRCA1 Mutation', 'BRCA-Mutated Ovarian Carcinoma', 'BRCA-Associated Breast Carcinoma', 'HRD Positive Advanced Ovarian Cancer']}, 'descriptionModule': {'briefSummary': '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.\n\nThe main question\\[s\\] it aims to answer are:\n\n* to evaluate the safety and tolerability of single agent and combination therapy\n* to determine the recommended dose for Phase 2 of single agent and combination therapy\n* to determine the pharmacokinetics of TNG348 as a single agent and in combination therapy\n* to evaluate the initial antineoplastic activity as a single agent and in combination therapy\n\nParticipants will receive study treatment until they experience an undesirable side effect, their disease progresses or until they withdraw consent.', 'detailedDescription': '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.\n\nIn Phase 1 (dose escalation), the single agent component will explore escalating oral doses of TNG348 administered alone and in combination with olaparib.\n\nParticipants 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.\n\nIn 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Is ≥18 years of age at the time of signature of the main study ICF.\n* Has ECOG performance status of 0 or 1.\n* Has advanced or metastatic solid tumor with measurable disease based on RECIST v1.1.\n* All participants must have documented BRCA 1/2 mutant or other HRD+ in solid tumor, which is identified through a validated sequencing test\n* Adequate organ and bone marrow function per local labs\n* Negative serum pregnancy test result at screening\n* Written informed consent must be obtained according to local guidelines\n\nExclusion Criteria:\n\n* Known allergies, hypersensitivity, or intolerance to TNG348, olaparib or its excipients\n* Uncontrolled intercurrent illness that will limit compliance with the study requirements\n* Currently participating in or has planned participation in a study of another investigational agent or device\n* Impairment of GI function or disease that may significantly alter the absorption of study drug\n* Active prior or concurrent malignancy.\n* Central nervous system metastases associated with progressive neurological symptoms\n* Participant with MDS\n* Clinically relevant cardiovascular disease\n* Participant with known active or chronic infection\n* A female patient who is pregnant or lactating'}, 'identificationModule': {'nctId': 'NCT06065059', 'briefTitle': 'Study to Evaluate TNG348 Alone and With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or HRD+ Solid Tumors', 'organization': {'class': 'INDUSTRY', 'fullName': 'Tango Therapeutics, Inc.'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'TNG348-C101'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Single Agent Dose Escalation', 'description': 'Participants with BRCA 1/2 mutant or HRD+ solid tumors will receive escalating doses of TNG348 to estimate the MTD', 'interventionNames': ['Drug: TNG348']}, {'type': 'EXPERIMENTAL', 'label': 'Combination Dose Escalation', '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', 'interventionNames': ['Drug: TNG348', 'Drug: Olaparib']}, {'type': 'EXPERIMENTAL', 'label': 'Single agent dose expansion in breast cancer', 'description': 'Participants with BRCA 1/2 mutant breast cancer will receive TNG348 at the identified RP2D', 'interventionNames': ['Drug: TNG348']}, {'type': 'EXPERIMENTAL', 'label': 'Single agent dose expansion in ovarian cancer', 'description': 'Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 at the identified RP2D', 'interventionNames': ['Drug: TNG348']}, {'type': 'EXPERIMENTAL', 'label': 'Combination therapy dose expansion in breast cancer', 'description': 'Participants with BRCA 1/2 mutant breast cancer will receive TNG348 in combination with olaparib at the identified RP2D', 'interventionNames': ['Drug: TNG348', 'Drug: Olaparib']}, {'type': 'EXPERIMENTAL', 'label': 'Combination therapy dose expansion in ovarian cancer', 'description': 'Participants with BRCA 1/2 mutant ovarian cancer will receive TNG348 in combination with olaparib at the identified RP2D', 'interventionNames': ['Drug: TNG348', 'Drug: Olaparib']}, {'type': 'EXPERIMENTAL', 'label': 'Combination therapy dose expansion in pancreatic or prostate cancer', 'description': 'Participants with BRCA 1/2 mutant pancreatic or prostate cancer will receive TNG348 in combination with olaparib at the identified RP2D', 'interventionNames': ['Drug: TNG348', 'Drug: Olaparib']}, {'type': 'EXPERIMENTAL', 'label': 'Combination therapy dose expansion in HRD+ advanced or metastatic solid tumors', 'description': 'Participants with HRD+ advanced or metastatic solid tumors will receive TNG348 in combination with olaparib at the identified RP2D', 'interventionNames': ['Drug: TNG348', 'Drug: Olaparib']}], 'interventions': [{'name': 'TNG348', 'type': 'DRUG', 'description': 'Ubiquitin Specific Peptidase 1 (USP1) inhibitor', 'armGroupLabels': ['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']}, {'name': 'Olaparib', 'type': 'DRUG', 'otherNames': ['Lynparza'], 'description': 'PARP inhibitor', 'armGroupLabels': ['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']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80218', 'city': 'Denver', 'state': 'Colorado', 'country': 'United States', 'facility': 'HealthONE', 'geoPoint': {'lat': 39.73915, 'lon': -104.9847}}, {'zip': '32763', 'city': 'Orange City', 'state': 'Florida', 'country': 'United States', 'facility': 'Mid Florida Cancer Centers', 'geoPoint': {'lat': 28.94888, 'lon': -81.29867}}, {'zip': '34232', 'city': 'Sarasota', 'state': 'Florida', 'country': 'United States', 'facility': 'Florida Cancer Specialists', 'geoPoint': {'lat': 27.33643, 'lon': -82.53065}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Dana Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '10016', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'New York University Langone Health', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas MD Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}], 'overallOfficials': [{'name': 'Adam Crystal, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Tango Therapeutics, Inc.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Tango Therapeutics, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}