Study of RP-6306 With FOLFIRI in Advanced Solid Tumors (MINOTAUR)

Phase 1 Study of the PKMYT1 Inhibitor RP-6306 in Combination With FOLFIRI for the Treatment of Advanced Solid Tumors

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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: RP-6306 (oral PKMYT1 inhibitor)

Detailed Description

To assess the safety and tolerability of RP-6306 in combination with FOLFIRI in patients with eligible, advanced solid tumors. Incidence and severity of treatment-emergent adverse events (TEAEs), laboratory assessments, vital signs, electrocardiograms (ECGs), and use of concomitant medications.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nathan Hawkey, MD, MBA; Phone Number: +1 857-340-5416; Email: clininfo@reparerx.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 2M9
      • Participating site # 2001
• Spain
  • Madrid, Spain
    • Site 5002
  • Madrid, Spain
    • Site 5003
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Participating Site # 3003
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Participating site #1019
  • Florida
    • Tampa, Florida, United States, 33612
      • Site 1022
  • New York
    • New York, New York, United States, 10032
      • Participating Site #1008
  • Texas
    • Houston, Texas, United States, 77030
      • Participating Site #1001
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Participating Site #1013

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 signature of the informed consent
• Confirmed advanced solid tumors resistant or refractory to standard treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• All patients must have locally advanced or metastatic CRC, GI, or esophageal cancer(s) and radiographic evidence of progressing disease.
• Measurable disease as per RECIST v1.1
• Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
• Acceptable hematologic and organ function at screening
• Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.

Exclusion Criteria:

• Inability to swallow and retain oral medications.
• Chemotherapy or small molecule antineoplastic agent given within 21 days or <5 half- lives, whichever is shorter, prior to first dose of study treatment.
• 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 study treatment dose.
• Uncontrolled, symptomatic brain metastases.
• Uncontrolled high blood pressure
• Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
• Moderate or severe hepatic impairment
• Cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥Class 2
• 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: RP-6306 in combination with FOLFIRI Dose Escalation; RP-6306 will be administered as oral capsules Multiple dose levels of RP-6306 (oral) and FOLFIRI (IV)	Drug: RP-6306 (oral PKMYT1 inhibitor); RP-6306 (Oral) in combination with FOLFIRI (IV); Other Names: FOLFIRI

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 and frequency of dose limiting toxicities, to determine safety and tolerability of RP-6306 in combination with FOLFIRI.	This data will be used to identify a recommended phase 2 dose (RP2D) and schedule of RP-6306 in combination with FOLFIRI	Up to 90 days after last administration of study intervention
To identify a maximum tolerated dose (MTD)	through evaluation of dose-limiting toxicities (DLTs) at or below a frequency of 25%.	Up to 90 days after last administration of study intervention

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	PK parameters of RP-6306, irinotecan, and SN-38	Through end of study, up to 2 months
Peak Plasma Concentration (Cmax) will be observed directly from data	PK parameters of RP-6306, irinotecan, and SN-38	Through end of study, up to 2 months
Minimum blood plasma concentration (Cmin) will be observed directly from data	PK parameters of RP-6306, irinotecan, and SN-38	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	PK parameters of RP-6306, irinotecan, and SN-38	Through end of study, up to 2 months
Best percent change in tumor size from baseline	To assess the preliminary efficacy of RP 6306 in combination with FOLFIRI in patients with molecularly selected, advanced solid tumors	objective response rate, best overall response rate, duration of response, clinical benefit rate, progression-free survival at 6 months, and overall survival at 12 months

Collaborators and Investigators

• Sponsor: Repare Therapeutics
• Investigators: Study Chair: Nathan Hawkey, Repare RX

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: RP-6306-03

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