Study of RP-6306 With FOLFIRI in Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

— MINOTAUR  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05147350
• Other study ID #: RP-6306-03
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 9, 2022
• Est. completion date: November 2026

Study information

• Verified date: March 2024
• Source: Repare Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: November 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• RP-6306 (oral PKMYT1 inhibitor)
RP-6306 (Oral) in combination with FOLFIRI (IV)

Locations

Country	Name	City	State
Canada	Participating site # 2001	Toronto	Ontario
Spain	Site 5002	Madrid
Spain	Site 5003	Madrid
United Kingdom	Participating Site # 3003	London
United States	Participating Site #1001	Houston	Texas
United States	Participating site #1019	Los Angeles	California
United States	Participating Site #1008	New York	New York
United States	Participating site #1013	Salt Lake City	Utah
United States	Site 1022	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Repare Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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