Study of RP-6306 With Gemcitabine 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 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
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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

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

Conditions
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Adult 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 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.

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 Dose Escalation<br>Multiple dose levels of RP-6306 and gemcitabine | Drug: RP-6306 (oral PKMYT1 inhibitor)<br>* RP-6306 in combination with gemcitabine<br>* Other names: Gemcitabine (IV);|

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 gemcitabine. | This data will be used to identify a recommended phase 2 dose (RP2D) and schedule of RP-6306 in combination with gemcitabine. | Up to 90 days after last administration of study intervention | 
| Number of dose limiting toxicities, as defined per protocol, that occur during the first cycle (21 days) of treatment at each dose level | 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 | Up to 90 days after last administration of study intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) from time 0 to 8 hours post dose | To assess PK parameters of RP-6306 in combination with gemcitabine | Through end of study, up to 2 months | 
| Peak Plasma Concentration (Cmax) will be observed directly from data | To assess PK parameters of RP-6306 in combination with gemcitabine | Through end of study, up to 2 months | 
| Minimum blood plasma concentration (Cmin) will be observed directly from data | To assess PK parameters of RP-6306 in combination with gemcitabine | 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 | To assess PK parameters of RP-6306 in combination with gemcitabine | Through end of study, up to 2 months | 
| 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 |