Ignite Creation Date:
2025-12-24 @ 11:16 PM
Ignite Modification Date:
2025-12-25 @ 8:53 PM
Study NCT ID:
NCT04855656
Status:
RECRUITING
Last Update Posted:
2025-08-06
First Post:
2021-04-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study of RP-6306 Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 364}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2021-04-30', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2026-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-08-01', 'studyFirstSubmitDate': '2021-04-09', 'studyFirstSubmitQcDate': '2021-04-19', 'lastUpdatePostDateStruct': {'date': '2025-08-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-04-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-06-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and Tolerability of RP-6306 either in monotherapy or in combination with RP-3500 or with Debio 0123 in patients with eligible advanced solid tumors', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by treatment-emergent adverse events (TEAEs), physical examinations (PEs), safety laboratory assessments, electrocardiograms (ECGs), and vital sign measurements'}, {'measure': 'To define the MTD of RP-6306 monotherapy, and determine a recommended Phase 2 dose (RP2D) and preferred schedule', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by the incidence of Dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data'}, {'measure': 'To define the MTD of RP-6306 in combination with RP-3500 or in combination with Debio 0123, and determine a recommended Phase 2 dose (RP2D) and preferred schedule', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by the incidence of dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data'}, {'measure': 'The relative bioavailability of RP-6306 capsule formulation as compared to RP-6306 tablet formulation in the fasted state', 'timeFrame': 'Time 0 (time of dosing) to 72 hours post-dose for each treatment condition', 'description': 'Assessed by the plasma concentrations of RP-6306 with calculation of pharmacokinetic (PK) parameters including maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) , for both formulations in the fasted state.'}, {'measure': 'The effect of food on the PK of tablet formulation of RP-6306 when administered in fed conditions compared to administration under fasted conditions', 'timeFrame': 'Time 0 (time of dosing) to 72 hours post-dose for each treatment condition', 'description': 'Assessed by the plasma concentrations of RP-6306 with calculation of the ratio of PK parameters (e.g., Cmax and AUC) between the tablet formulation under fasted and fed state.'}, {'measure': 'To assess the safety and tolerability of RP-6306 tablets in combination with RP-3500, confirm the MTD of RP-6306 tablets in combination with RP-3500, and determine a RP2D and preferred schedule', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by DLTs, TEAEs, safety laboratory assessments, the incidence of DLTs and the incidence and severity of cumulative safety data'}], 'secondaryOutcomes': [{'measure': 'The plasma concentrations of RP-6306 monotherapy (capsule formulation) in the fasted and fed states', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by the plasma concentrations of RP-6306 with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate'}, {'measure': 'To assess the relationship between pharmacodynamic biomarkers and PK of RP-6306 at different dose levels and/or schedules', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by evaluation of biomarkers in pre- and on-treatment biopsies, and circulating tumor DNA (ctDNA) dynamics during treatment'}, {'measure': 'The plasma concentrations of RP-6306 and RP-3500 when dosed in combination', 'timeFrame': 'Up to 90 days after last administration of study intervention', 'description': 'Assessed by the plasma concentrations of RP-6306 and RP-3500 with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate for each analyte'}, {'measure': 'To assess preliminary anti-tumor activity achieved with RP-6306 monotherapy, RP-6306 in combination with RP-3500 or RP-6306 in combination with Debio 0123', 'timeFrame': 'Through Study Completion, an average of 1 year', 'description': 'Measured by best percent change in tumor size from baseline, objective response rate (ORR), overall response rate, tumor marker response, duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS).'}, {'measure': 'To assess the safety and anti-tumor effects of RP-6306 capsule + RP-3500', 'timeFrame': 'Through Study Completion, an average of 1 year', 'description': 'As measure by TEAEs, safety laboratory assessments, Best percent change in tumor size from baseline, ORR, overall response rate, DOR, CBR, tumor marker response, PFS'}, {'measure': 'To further characterize the PK of RP-6306 tablets and assess preliminary anti-tumor', 'timeFrame': 'Through Study Completion, an average of 1 year', 'description': 'Measured by Plasma concentrations of RP-6306 with calculation of Cmax, Tmax, AUC, elimination t1/2, and other PK parameters as appropriate, Best percent change in tumor size from baseline, ORR, overall response rate, DOR, CBR, tumor marker response, PFS'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Advanced Solid Tumor']}, 'descriptionModule': {'briefSummary': 'The primary purpose of this study is to assess the safety and tolerability of RP-6306 alone and in combination with RP-3500 or in combination with Debio 0123 in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) and assess preliminary anti-tumor activity.', 'detailedDescription': 'Phase 1/1b, multi-center, open-label, dose-escalation study to:\n\n* Evaluate the safety profile and MTD of RP-6306 alone and in combination with RP-3500 or in combination with Debio 0123 when administered orally to establish the recommended Phase 2 dose and schedule\n* Characterize the PK and pharmacodynamics of RP-6306 alone and in combination with RP-3500 or in combination with Debio 0123\n* Assess preliminary anti-tumor activity associated with RP-6306 alone and in combination with RP-3500 or in combination with Debio 0123'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Male or female and ≥12 years-of-age at the time of informed consent.\n* Lansky performance status ≥50% for patients ≤16 years of age, or ECOG score of 0, 1, (or 2 for module 1) for patients \\>16 years of age.\n* Locally advanced or metastatic resistant or refractory solid tumors.\n* Patients \\<18 years of age must weigh at least 40 kg.\n* Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible\n* Next generation sequencing (NGS) report obtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarker.\n* CCNE1 amplification (non-equivocal) as determined by either a tumor or plasma NGS test, or FISH\n* FBXW7 deleterious mutations identified by either a tumor or plasma NGS test\n* PPP2R1A deleterious mutations identified by either a tumor or plasma NGS test\n* Measurable disease as per RECIST v1.1. For certain modules, patients with prostate cancer or ovarian cancer that have non-measurable disease but have elevated tumor markers (PSA or CA-125, respectively) can also be eligible\n* Ability to swallow and retain oral medications.\n* Acceptable hematologic and organ function at screening.\n* Negative pregnancy test (serum) for women of childbearing potential (WOCBP) at Screening.\n* Resolution of all toxicities of prior therapy or surgical procedures.\n* Any prior radiation must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment.\n\nExclusion Criteria:\n\n* Chemotherapy or small molecule antineoplastic agent given within 21 days or \\<5 half-lives, whichever is shorter, prior to first dose of study drug.\n* History or current condition, therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation for the full duration of the study treatment.\n* Patients who are pregnant or breastfeeding.\n* Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the participating patient's safety.\n* Major surgery within 4 weeks prior to first dose of RP-6306.\n* Uncontrolled, symptomatic brain metastases.\n* Uncontrolled hypertension.\n* Certain prior anti-cancer therapy\n* Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol."}, 'identificationModule': {'nctId': 'NCT04855656', 'acronym': 'MYTHIC', 'briefTitle': 'Study of RP-6306 Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors', 'organization': {'class': 'INDUSTRY', 'fullName': 'Repare Therapeutics'}, 'officialTitle': 'Phase 1/1b Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-6306 Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors', 'orgStudyIdInfo': {'id': 'RP-6306-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Phase 1: RP-6306 Single-Agent, Dose Escalation and Food-effect Study', 'description': 'Patients receive RP-6306 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.', 'interventionNames': ['Drug: RP-6306']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1: RP-6306 in combination with RP-3500, Dose Escalation Study', 'description': 'Patients receive RP-6306 with RP-3500 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.', 'interventionNames': ['Drug: RP-6306', 'Drug: RP-3500']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1: RP-6306 in combination with Debio 0123, Dose Escalation Study', 'description': 'Patients receive RP-6306 with Debio 0123 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.', 'interventionNames': ['Drug: RP-6306', 'Drug: Debio0123']}], 'interventions': [{'name': 'RP-6306', 'type': 'DRUG', 'description': 'Oral PKMYT1 Inhibitor', 'armGroupLabels': ['Phase 1: RP-6306 Single-Agent, Dose Escalation and Food-effect Study', 'Phase 1: RP-6306 in combination with Debio 0123, Dose Escalation Study', 'Phase 1: RP-6306 in combination with RP-3500, Dose Escalation Study']}, {'name': 'RP-3500', 'type': 'DRUG', 'description': 'Oral ATR Inhibitor', 'armGroupLabels': ['Phase 1: RP-6306 in combination with RP-3500, Dose Escalation Study']}, {'name': 'Debio0123', 'type': 'DRUG', 'description': 'Oral WEE1 Inhibitor', 'armGroupLabels': ['Phase 1: RP-6306 in combination with Debio 0123, Dose Escalation Study']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85054', 'city': 'Phoenix', 'state': 'Arizona', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1016, Mayo Clinic', 'geoPoint': {'lat': 33.44838, 'lon': -112.07404}}, {'zip': '90095', 'city': 'Los Angeles', 'state': 'California', 'status': 'COMPLETED', 'country': 'United States', 'facility': '# 1019, UCLA, Westwood Cancer Center', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '94158', 'city': 'San Francisco', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1025, University of California San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '06520', 'city': 'New Haven', 'state': 'Connecticut', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1012, Yale', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '32224', 'city': 'Jacksonville', 'state': 'Florida', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1017, Mayo Clinic', 'geoPoint': {'lat': 30.33218, 'lon': -81.65565}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1002, Dana Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '49503', 'city': 'Grand Rapids', 'state': 'Michigan', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1023, START Midwest', 'geoPoint': {'lat': 42.96336, 'lon': -85.66809}}, {'zip': '63130', 'city': 'St Louis', 'state': 'Missouri', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1011, Washington University', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '11042', 'city': 'New Hyde Park', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1032, Northwell Health Cancer Institute', 'geoPoint': {'lat': 40.7351, 'lon': -73.68791}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'status': 'ACTIVE_NOT_RECRUITING', 'country': 'United States', 'facility': '#1008, Columbia University', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1004, Memorial Sloan Kettering Cancer Institute', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'status': 'COMPLETED', 'country': 'United States', 'facility': '#1010, University of Pennsylvania', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '02903', 'city': 'Providence', 'state': 'Rhode Island', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1007, Rhode Island Hospital', 'geoPoint': {'lat': 41.82399, 'lon': -71.41283}}, {'zip': '02903', 'city': 'Providence', 'state': 'Rhode Island', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1030, Women & Infants Hospital of Rhode Island', 'geoPoint': {'lat': 41.82399, 'lon': -71.41283}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1001, The University of Texas M.D. Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1013, The University of Utah', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'zip': '22903', 'city': 'Charlottesville', 'state': 'Virginia', 'status': 'RECRUITING', 'country': 'United States', 'facility': '#1027, University of Virginia', 'geoPoint': {'lat': 38.02931, 'lon': -78.47668}}, {'zip': 'M5G 1X8', 'city': 'Toronto', 'state': 'Ontario', 'status': 'COMPLETED', 'country': 'Canada', 'facility': '#2002, The Hospital for Sick Children', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': 'M5G 2C1', 'city': 'Toronto', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'facility': '#2001, Princess Margaret Cancer Centre', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': 'H4A 3J1', 'city': 'Montreal', 'state': 'Quebec', 'status': 'COMPLETED', 'country': 'Canada', 'facility': '#2003, The Research Institute of the McGill University Health Centre', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'city': 'Copenhagen', 'status': 'RECRUITING', 'country': 'Denmark', 'facility': '#4001, Rigshospitalet - Blegdamsvej', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}, {'zip': 'W1G 6AD', 'city': 'London', 'status': 'RECRUITING', 'country': 'United Kingdom', 'facility': '#3003, Sarah Cannon Research Institute', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'centralContacts': [{'name': 'Repare Therapeutics Medical Monitor, MD, MBA', 'role': 'CONTACT', 'email': 'clininfo@reparerx.com', 'phone': '+1 (857) 340-5402'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Repare Therapeutics', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Debiopharm International SA', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}