Study of RP-6306 With FOLFIRI in Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: RP-6306 (oral PKMYT1 inhibitor)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Dose Escalation and expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: RP-6306 in combination with FOLFIRI Dose Escalation<br>RP-6306 will be administered as oral capsules Multiple dose levels of RP-6306 (oral) and FOLFIRI (IV) | Drug: RP-6306 (oral PKMYT1 inhibitor)<br>* RP-6306 (Oral) in combination with FOLFIRI (IV)<br>* Other names: FOLFIRI;|

What is the study measuring?
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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 |
| --- | --- | --- |
| preliminary efficacy | To assess the preliminary efficacy of RP-6306 in combination with FOLFIRI using RECIST | Through study completion, up to 12 months | 
| 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 |