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

Sponsor
Repare Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04855656
Collaborator
(none)
120
Enrollment
12
Locations
2
Arms
36
Anticipated Duration (Months)
10
Patients Per Site
0.3
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 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
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

Study Design

Study Type:
Interventional
Anticipated 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 :
Apr 30, 2021
Anticipated Primary Completion Date :
Oct 30, 2023
Anticipated Study Completion Date :
Apr 30, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Safety and Tolerability of RP-6306 in patients with advanced solid tumors as assessed by NCI CTCAE v5.0 [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 [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 [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 [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. [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. [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. [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. [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. [Through Study Completion, an average of 1 year]

Eligibility Criteria

Criteria

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Participating Site # 1012 New Haven Connecticut United States 06520
2 Participating site # 1002 Boston Massachusetts United States 02215
3 Participating site #1011 Saint Louis Missouri United States 63130
4 Participating Site # 1008 New York New York United States 10032
5 Participating Site # 1004 New York New York United States 10065
6 Participating Site # 1010 Philadelphia Pennsylvania United States 19104
7 Participating Site # 1007 Providence Rhode Island United States 02903
8 Participating Site # 1001 Houston Texas United States 77030
9 Participating Site #1013 Salt Lake City Utah United States 84112
10 Participating site # 2002 Toronto Ontario Canada M5G 1X8
11 Participating site #2001 Toronto Ontario Canada M5G 2C1
12 Participating Site #4001 Copenhagen Denmark

Sponsors and Collaborators

  • Repare Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Repare Therapeutics
ClinicalTrials.gov Identifier:
NCT04855656
Other Study ID Numbers:
  • RP-6306-01
First Posted:
Apr 22, 2021
Last Update Posted:
May 2, 2022
Last Verified:
Mar 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

Study Results

No Results Posted as of May 2, 2022