Study of RP-6306 With Gemcitabine in Advanced Solid Tumors

Phase 1 Study of the PKMYT1 Inhibitor RP-6306 in Combination With Gemcitabine for the Treatment of Advanced Solid Tumors (MAGNETIC Study)

The primary purpose of this study is to assess the safety and tolerability of RP-6306 in combination gemcitabine, in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-6306 in combination with gemcitabine, identify a recommended phase 2 dose (RP2D) and preferred schedule, examine preliminary pharmacokinetics (PK) and assess anti-tumor activity.

Study Overview

• Status: Terminated
• Conditions: Adult Solid Tumor
• Intervention / Treatment: Drug: RP-6306 (oral PKMYT1 inhibitor)

Detailed Description

Phase 1, multi-center, open-label, dose-escalation study to:

• Evaluate the safety profile and MTD of RP-6306 with gemcitabine to establish the RP2D and schedule
• Characterize the PK and pharmacodynamics of RP-6306 with gemcitabine
• Assess preliminary anti-tumor activity associated with RP-6306 with gemcitabine

The Sponsor of the study has changed from 'Repare Therapeutics' to 'Debiopharm International SA' in the United States.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • # 2001, Princess Margaret Cancer Centre
• United Kingdom
  • London, United Kingdom
    • # 3003, Sarah Cannon Research Institute
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • # 1018, Mayo Clinic
  • California
    • Los Angeles, California, United States, 90095
      • # 1019, UCLA, Westwood Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • # 1017, Mayo Clinic
    • Tampa, Florida, United States, 33612
      • # 1022, Moffitt Cancer Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • # 1023, START Midwest
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • # 1016, Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • # 1008, Columbia University
    • New York, New York, United States, 10065
      • # 1004, Memorial Sloan Kettering Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • # 1010, University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female and ≥18 years-of-age at the time of informed consent.
• ECOG Performance status 0 or 1.
• Locally advanced or metastatic resistant or refractory solid tumors.
• Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible.
• Measurable disease as per RECIST v1.1.
• Ability to swallow and retain oral medications.
• Acceptable hematologic and organ function at screening.
• Negative pregnancy test (serum) for women of childbearing potential (WOCBP) at Screening.
• Resolution of all toxicities of prior therapy or surgical procedures.
• Life expectancy ≥12 weeks after the start of the treatment

Exclusion Criteria:

• Chemotherapy or small molecule antineoplastic agent given within 21 days or <5 half- lives, whichever is shorter, prior to first dose of study drug.
• 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.
• Patients who are pregnant or breastfeeding.
• Known sensitivity to any of the ingredients of RP-6306 or gemcitabine.
• 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.
• Major surgery within 4 weeks prior to first dose of RP-6306 and gemcitabine.
• Uncontrolled, symptomatic brain metastases.
• Uncontrolled hypertension.
• Moderate or severe hepatic impairment
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose Escalation; Multiple dose levels of RP-6306 and gemcitabine	Drug: RP-6306 (oral PKMYT1 inhibitor); RP-6306 in combination with gemcitabine; Other Names: Gemcitabine (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With of Treatment-related Adverse Event Data Per CTCAE v5.0 Criteria to Determine Safety and Tolerability of RP-6306 in Combination With Gemcitabine.	Incidence of grade 3 and above Treatment Related Emergent Adverse Events (TRAEs)	Start of treatment to 30 days post last dose. up to 1.5 years
Number of Dose Limiting Toxicities, as Defined Per Protocol, That Occur During the First Cycle (21 Days) of Treatment at Each Dose Level	Evaluation of dose-limiting toxicities (DLTs) at or below a frequency of 25%	During 21 days from the initiation of the study treatment (C1D1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) from time 0 to 8 hours post dose	To assess PK parameters of RP-6306 in combination with gemcitabine	Through end of study, up to 2 months
Peak Plasma Concentration (Cmax) will be observed directly from data	To assess PK parameters of RP-6306 in combination with gemcitabine	Through end of study, up to 2 months
Minimum blood plasma concentration (Cmin) will be observed directly from data	To assess PK parameters of RP-6306 in combination with gemcitabine	Through end of study, up to 2 months
Time take to reach Cmax (Tmax) will be observed directly from data as time of first occurrence	To assess PK parameters of RP-6306 in combination with gemcitabine	Through end of study, up to 2 months
Overall response rate (ORR) of RP-6306 in combination with gemcitabine will be measured using RECIST v1.1 criteria		Through study completion, up to 12 months

Collaborators and Investigators

• Sponsor: Debiopharm International SA
• Collaborators: Repare Therapeutics
• Investigators: Study Director: Jen Truong, MD, MPH, Repare Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): August 28, 2024
• Study Completion (Actual): August 28, 2024

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine
• Other Study ID Numbers: RP-6306-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No