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Study of RP-6306 Alone or in Combination With RP-3500 in Patients With Advanced Solid Tumors (MYTHIC)

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ClinicalTrials.gov Identifier: NCT04855656
Recruitment Status : Recruiting
First Posted : April 22, 2021
Last Update Posted : May 2, 2022
Sponsor:
Information provided by (Responsible Party):
Repare Therapeutics

Brief Summary:
The primary purpose of this study is to assess the safety and tolerability of RP-6306 alone and in combination with RP-3500 in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) and assess preliminary anti-tumor activity.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: RP-6306 Drug: RP-3500 Phase 1

Detailed Description:

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

  • Evaluate the safety profile and MTD of RP-6306 alone and in combination with RP-3500 when administered orally to establish the recommended Phase 2 dose and schedule
  • Characterize the PK and pharmacodynamics of RP-6306 alone and in combination with RP-3500
  • Assess preliminary anti-tumor activity associated with RP-6306 alone and in combination with RP-3500

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-6306 Alone or in Combination With RP-3500 in Patients With Advanced Solid Tumors
Actual Study Start Date : April 30, 2021
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : April 30, 2024

Arm Intervention/treatment
Experimental: Phase 1: RP-6306 Single-Agent, Dose Escalation and Food-effect Study
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.
Drug: RP-6306
Oral PKMYT1 Inhibitor

Experimental: Phase 1: RP-6306 in combination with RP-3500, Dose Escalation Study
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.
Drug: RP-6306
Oral PKMYT1 Inhibitor

Drug: RP-3500
Oral ATR Inhibitor




Primary Outcome Measures :
  1. Safety and Tolerability of RP-6306 in patients with advanced solid tumors as assessed by NCI CTCAE v5.0 [ Time Frame: Up to 90 days after last administration of study intervention ]
  2. To define the MTD of RP-6306 monotherapy, and determine a recommended Phase 2 dose (RP2D) and preferred schedule [ Time Frame: Up to 90 days after last administration of study intervention ]
  3. Safety and Tolerability of RP-6306 in combination with RP-3500 in patients with advanced solid tumors as assessed by NCI CTCAE v5.0 [ Time Frame: Up to 90 days after last administration of study intervention ]
  4. To define the MTD of RP-6306 in combination with RP-3500, and determine a recommended Phase 2 dose (RP2D) and preferred schedule [ Time Frame: Up to 90 days after last administration of study intervention ]

Secondary Outcome Measures :
  1. To assess the plasma concentrations of RP-6306 monotherapy in the fasted and fed states. [ Time Frame: through study completion, an average of 1 year ]
  2. To assess the correlation between RP-6306 dose (mg) and degree of inhibition of phospho-CDK1 signal by immunohistochemistry. [ Time Frame: for the first 3 months on treatment ]
  3. To assess the percent of patients with a response to RP-6306 monotherapy per RECIST v1.1 criteria. [ Time Frame: Through Study Completion, an average of 1 year ]
  4. To assess the correlation between RP-6306 and RP-3500 dose (mg) and degree of gamma-H2AX induction by immunohistochemistry. [ Time Frame: for the first 3 months on treatment ]
  5. To assess the percent of patients with a response to RP-6306 and RP-3500 per RECIST v1.1 criteria. [ Time Frame: Through Study Completion, an average of 1 year ]


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female and ≥12 years-of-age at the time of informed consent.
  • Lansky performance status ≥50% for patients ≤16 years of age, or ECOG score of 0, 1, or 2 for patients >16 years of age.
  • Locally advanced or metastatic resistant or refractory solid tumors.
  • Patients <18 years of age must weigh at least 40 kg.
  • Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible
  • Next generation sequencing (NGS) report obtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarker.
  • 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.
  • 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.

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.
  • 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.
  • Uncontrolled, symptomatic brain metastases.
  • Uncontrolled hypertension.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04855656


Contacts
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Contact: Jen Truong, MD, MPH 857-340-5439 jtruong@reparerx.com

Locations
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United States, Connecticut
Participating Site # 1012 Recruiting
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Participating site # 1002 Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Participating site #1011 Recruiting
Saint Louis, Missouri, United States, 63130
United States, New York
Participating Site # 1008 Recruiting
New York, New York, United States, 10032
Participating Site # 1004 Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Participating Site # 1010 Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Participating Site # 1007 Recruiting
Providence, Rhode Island, United States, 02903
United States, Texas
Participating Site # 1001 Recruiting
Houston, Texas, United States, 77030
United States, Utah
Participating Site #1013 Recruiting
Salt Lake City, Utah, United States, 84112
Canada, Ontario
Participating site # 2002 Recruiting
Toronto, Ontario, Canada, M5G 1X8
Participating site #2001 Recruiting
Toronto, Ontario, Canada, M5G 2C1
Denmark
Participating Site #4001 Recruiting
Copenhagen, Denmark
Sponsors and Collaborators
Repare Therapeutics
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Responsible Party: Repare Therapeutics
ClinicalTrials.gov Identifier: NCT04855656    
Other Study ID Numbers: RP-6306-01
First Posted: April 22, 2021    Key Record Dates
Last Update Posted: May 2, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms