Study of RP-6306 With Gemcitabine 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 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

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Phase 1 Dose Escalation	RP-6306 (oral PKMYT1 inhibitor)	Multiple dose levels of RP-6306 and gemcitabine

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 gemcitabine.	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 gemcitabine.
Number of dose limiting toxicities, as defined per protocol, that occur during the first cycle (21 days) of treatment at each dose level	Up to 90 days after last administration of study intervention	Frequency and severity of treatment-related adverse events per CTCAE v5.0 among all patients treated with at least one dose of RP-6306 and gemcitabine

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR) of RP-6306 in combination with gemcitabine will be measured using RECIST v1.1 criteria	Through study completion, up to 12 months
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	To assess PK parameters of RP-6306 in combination with gemcitabine
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	To assess PK parameters of RP-6306 in combination with gemcitabine
Peak Plasma Concentration (Cmax) will be observed directly from data	Through end of study, up to 2 months	To assess PK parameters of RP-6306 in combination with gemcitabine
Minimum blood plasma concentration (Cmin) will be observed directly from data	Through end of study, up to 2 months	To assess PK parameters of RP-6306 in combination with gemcitabine

Locations (11): Participating site # 1017
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Jacksonville, Florida, United States
Participating Site # 1023
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Grand Rapids, Michigan, United States
Participating Site # 1008
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New York, New York, United States
Participating Site # 1004
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New York, New York, United States
Participating site # 3003
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London, United Kingdom
Participating site # 1018
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Phoenix, Arizona, United States
Participating site # 1019
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Los Angeles, California, United States
Participating Site # 1010
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Philadelphia, Pennsylvania, United States
Participating site # 2001
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Toronto, Ontario, Canada
Participating site # 1016
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Rochester, Minnesota, United States
Participating Site #1022
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Tampa, Florida, United States