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Study of RP-6306 With Gemcitabine in Advanced Solid Tumors

Sponsor
Repare Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05147272
Collaborator
(none)
104
Enrollment
5
Locations
1
Arm
23.5
Anticipated Duration (Months)
20.8
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: RP-6306 (oral PKMYT1 inhibitor)
 Phase 1

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
104 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
Dose Escalation and ExpansionDose Escalation and Expansion
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1 Study of the PKMYT1 Inhibitor RP-6306 in Combination With Gemcitabine for the Treatment of Advanced Solid Tumors (MAGNETIC Study)
Actual Study Start Date :
Dec 16, 2021
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of patients with of treatment-related adverse event data per CTCAE v5.0 criteria and frequency of dose limiting toxicities, to determine safety and tolerability of RP-6306 in combination with gemcitabine. [Up to 90 days after last administration of study intervention]

      This data will be used to identify a recommended phase 2 dose (RP2D) and schedule of RP-6306 in combination with gemcitabine.

    2. Number of dose limiting toxicities, as defined per protocol, that occur during the first cycle (21 days) of treatment at each dose level [Up to 90 days after last administration of study intervention]

      Frequency and severity of treatment-related adverse events per CTCAE v5.0 among all patients treated with at least one dose of RP-6306 and gemcitabine

    Secondary Outcome Measures

    1. Area under the plasma concentration versus time curve (AUC) from time 0 to 8 hours post dose [Through end of study, up to 2 months]

      To assess PK parameters of RP-6306 in combination with gemcitabine

    2. Peak Plasma Concentration (Cmax) will be observed directly from data [Through end of study, up to 2 months]

      To assess PK parameters of RP-6306 in combination with gemcitabine

    3. Minimum blood plasma concentration (Cmin) will be observed directly from data [Through end of study, up to 2 months]

      To assess PK parameters of RP-6306 in combination with gemcitabine

    4. Time take to reach Cmax (Tmax) will be observed directly from data as time of first occurrence [Through end of study, up to 2 months]

      To assess PK parameters of RP-6306 in combination with gemcitabine

    5. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Participating Site # 1023 Grand Rapids Michigan United States 49546
    2 Participating Site # 1008 New York New York United States 10032
    3 Participating Site # 1004 New York New York United States 10065
    4 Participating Site # 1010 Philadelphia Pennsylvania United States 19104
    5 Participating site # 2001 Toronto Ontario Canada M5G 2C1

    Sponsors and Collaborators

    • Repare Therapeutics

    Investigators

    • Study Director: Jen Truong, MD, MPH, Repare Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Repare Therapeutics
    ClinicalTrials.gov Identifier:
    NCT05147272
    Other Study ID Numbers:
    • RP-6306-02
    First Posted:
    Dec 7, 2021
    Last Update Posted:
    May 18, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms
    Gemcitabine

    Study Results

    No Results Posted as of May 18, 2022