Clinical trial NCT05147272: Study of RP-6306 With Gemcitabine in Advanced Solid Tumors
Official title: Phase 1 Study of the PKMYT1 Inhibitor RP-6306 in Combination With Gemcitabine for the Treatment of Advanced Solid Tumors (MAGNETIC Study)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Adult Solid Tumor
Lead sponsor: Repare Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 67
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 in combination gemcitabine, in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-6306 in combination with gemcitabine, identify a recommended phase 2 dose (RP2D) and preferred schedule, examine preliminary pharmacokinetics (PK) and assess anti-tumor activity.

Detailed description: Phase 1, multi-center, open-label, dose-escalation study to:

* Evaluate the safety profile and MTD of RP-6306 with gemcitabine to establish the RP2D and schedule
* Characterize the PK and pharmacodynamics of RP-6306 with gemcitabine
* Assess preliminary anti-tumor activity associated with RP-6306 with gemcitabine

Eligibility criteria: Inclusion Criteria:

* Male or female and ≥18 years-of-age at the time of informed consent.
* ECOG Performance status 0 or 1.
* Locally advanced or metastatic resistant or refractory solid tumors.
* Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible.
* Measurable disease as per RECIST v1.1.
* Ability to swallow and retain oral medications.
* Acceptable hematologic and organ function at screening.
* Negative pregnancy test (serum) for women of childbearing potential (WOCBP) at Screening.
* Resolution of all toxicities of prior therapy or surgical procedures.
* Life expectancy ≥12 weeks after the start of the treatment

Exclusion Criteria:

* Chemotherapy or small molecule antineoplastic agent given within 21 days or \<5 half- lives, whichever is shorter, prior to first dose of study drug.
* 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.
* Known sensitivity to any of the ingredients of RP-6306 or gemcitabine.
* 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 dose of RP-6306 and gemcitabine.
* Uncontrolled, symptomatic brain metastases.
* Uncontrolled hypertension.
* Moderate or severe hepatic impairment
* 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 gemcitabine.
timeFrame: Up to 90 days after last administration of study intervention
measure: Number of dose limiting toxicities, as defined per protocol, that occur during the first cycle (21 days) of treatment at each dose level
timeFrame: Up to 90 days after last administration of study intervention
Secondary outcomes:
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
measure: Overall response rate (ORR) of RP-6306 in combination with gemcitabine will be measured using RECIST v1.1 criteria
timeFrame: Through study completion, up to 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: # 1018, Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: # 1019, UCLA, Westwood Cancer Center
state: California
city: Jacksonville
country: United States
facility: # 1017, Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: # 1022, Moffitt Cancer Center
state: Florida
city: Grand Rapids
country: United States
facility: # 1023, START Midwest
state: Michigan
city: Rochester
country: United States
facility: # 1016, Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: # 1008, Columbia University
state: New York
city: New York
country: United States
facility: # 1004, Memorial Sloan Kettering Cancer Institute
state: New York
city: Philadelphia
country: United States
facility: # 1010, University of Pennsylvania
state: Pennsylvania
city: Toronto
country: Canada
facility: # 2001, Princess Margaret Cancer Centre
state: Ontario
city: London
country: United Kingdom
facility: # 3003, Sarah Cannon Research Institute
Study officials:
References: