Study of RP-6306 With Gemcitabine in Advanced Solid Tumors

Adult Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05147272
• Other study ID #: RP-6306-02
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 16, 2021
• Est. completion date: April 30, 2025

Study information

• Verified date: January 2024
• Source: Repare Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 104
• Est. completion date: April 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Adult Solid Tumor
• Neoplasms

Intervention

Drug:
• RP-6306 (oral PKMYT1 inhibitor)
RP-6306 in combination with gemcitabine

Locations

Country	Name	City	State
Canada	Participating site # 2001	Toronto	Ontario
United Kingdom	Participating site # 3003	London
United States	Participating Site # 1023	Grand Rapids	Michigan
United States	Participating site # 1017	Jacksonville	Florida
United States	Participating site # 1019	Los Angeles	California
United States	Participating Site # 1004	New York	New York
United States	Participating Site # 1008	New York	New York
United States	Participating Site # 1010	Philadelphia	Pennsylvania
United States	Participating site # 1018	Phoenix	Arizona
United States	Participating site # 1016	Rochester	Minnesota
United States	Participating Site #1022	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Repare Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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