Study of RP-6306 with FOLFIRI in Advanced Solid Tumors

Phase 1

Active, not recruiting

Brief 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.

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.

Recruitment & 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.

Arm && Interventions

Group	Intervention	Description
Phase 1: RP-6306 in combination with FOLFIRI Dose Escalation	RP-6306 (oral PKMYT1 inhibitor)	RP-6306 will be administered as oral capsules Multiple dose levels of RP-6306 (oral) and FOLFIRI (IV)

Primary Outcome Measures

Name	Time	Method
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.	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 FOLFIRI
To identify a maximum tolerated dose (MTD)	Up to 90 days after last administration of study intervention	through evaluation of dose-limiting toxicities (DLTs) at or below a frequency of 25%.

Secondary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax) will be observed directly from data	Through end of study, up to 2 months	PK parameters of RP-6306, irinotecan, and SN-38
Best percent change in tumor size from baseline	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	To assess the preliminary efficacy of RP 6306 in combination with FOLFIRI in patients with molecularly selected, advanced solid tumors
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	PK parameters of RP-6306, irinotecan, and SN-38
Minimum blood plasma concentration (Cmin) will be observed directly from data	Through end of study, up to 2 months	PK parameters of RP-6306, irinotecan, and SN-38
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	PK parameters of RP-6306, irinotecan, and SN-38

Locations (9): Site 1022
🇺🇸
Tampa, Florida, United States
Site 5002
🇪🇸
Madrid, Spain
Site 5003
🇪🇸
Madrid, Spain
Participating site #1019
🇺🇸
Los Angeles, California, United States
Participating site # 2001
🇨🇦
Toronto, Ontario, Canada
Participating Site # 3003
🇬🇧
London, United Kingdom
Participating Site #1008
🇺🇸
New York, New York, United States
Participating Site #1001
🇺🇸
Houston, Texas, United States
Participating site #1013
🇺🇸
Salt Lake City, Utah, United States