Study of RP-6306 With FOLFIRI in Advanced Solid Tumors

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.

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.

The Sponsor of the study has changed from 'Repare Therapeutics' to 'Debiopharm International SA' in the United States.

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.