Clinical trial NCT05147350: Study of RP-6306 With FOLFIRI in Advanced Solid Tumors
Official title: Phase 1 Study of the PKMYT1 Inhibitor RP-6306 in Combination With FOLFIRI for the Treatment of Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Repare Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation and expansion
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Up to 90 days after last administration of study intervention
measure: To identify a maximum tolerated dose (MTD)
timeFrame: Up to 90 days after last administration of study intervention
Secondary outcomes:
measure: Best percent change in tumor size from baseline
timeFrame: 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
measure: Area under the plasma concentration versus time curve (AUC) from time 0 to 8 hours post dose
timeFrame: Through end of study, up to 2 months
measure: Peak Plasma Concentration (Cmax) will be observed directly from data
timeFrame: Through end of study, up to 2 months
measure: Minimum blood plasma concentration (Cmin) will be observed directly from data
timeFrame: Through end of study, up to 2 months
measure: Time take to reach Cmax (Tmax) will be observed directly from data as time of first occurrence
timeFrame: Through end of study, up to 2 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: #1019, UCLA, Westwood Cancer Center
state: California
city: Tampa
country: United States
facility: #1022, Moffitt Cancer Center
state: Florida
city: New York
country: United States
facility: #1008, Columbia University
state: New York
city: Houston
country: United States
facility: #1001, The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: #1013, The University of Utah, Huntsman Cancer Center
state: Utah
city: Toronto
country: Canada
facility: # 2001, Princess Margaret Cancer Centre
state: Ontario
city: Madrid
country: Spain
facility: # 5002, South Texas Accelerated Research Therapeutics
city: Madrid
country: Spain
facility: # 5003, Hospital Universitario HM Sanchinarro
city: London
country: United Kingdom
facility: # 3003, Sarah Cannon Research Institute
Study officials:
References: