Study of Lunresertib Alone or in Combination With RP-3500... | NCT04855656

ID	Type	Description	Link
RP-6306-01	Other Identifier	Repare Therapeutics

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1: Lunresertib Single-Agent, Dose Escalation and Food-effect Study	Experimental	Patients receive lunresertib orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.	Drug: Lunresertib
Phase 1: Lunresertib in combination with RP-3500, Dose Escalation Study	Experimental	Patients receive lunresertib with RP-3500 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.	Drug: Lunresertib Drug: RP-3500
Phase 1: Lunresertib in combination with Debio 0123, Dose Escalation Study	Experimental	Patients receive lunresertib with Debio 0123 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.	Drug: Lunresertib Drug: Debio0123

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lunresertib	Drug	Oral PKMYT1 Inhibitor	Phase 1: Lunresertib Single-Agent, Dose Escalation and Food-effect Study Phase 1: Lunresertib in combination with Debio 0123, Dose Escalation Study

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety and Tolerability of lunresertib either in monotherapy or in combination with RP-3500 or with Debio 0123 in patients with eligible advanced solid tumors	Assessed by treatment-emergent adverse events (TEAEs), physical examinations (PEs), safety laboratory assessments, electrocardiograms (ECGs), and vital sign measurements	Up to 90 days after last administration of study intervention
To define the MTD of lunresertib monotherapy, and determine a recommended Phase 2 dose (RP2D) and preferred schedule	Assessed by the incidence of Dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data	Up to 90 days after last administration of study intervention
To define the MTD of lunresertib in combination with RP-3500 or in combination with Debio 0123, and determine a recommended Phase 2 dose (RP2D) and preferred schedule	Assessed by the incidence of dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data	Up to 90 days after last administration of study intervention
The relative bioavailability of lunresertib capsule formulation as compared to lunresertib tablet formulation in the fasted state	Assessed by the plasma concentrations of lunresertib with calculation of pharmacokinetic (PK) parameters including maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) , for both formulations in the fasted state.	Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
The effect of food on the PK of tablet formulation of lunresertib when administered in fed conditions compared to administration under fasted conditions	Assessed by the plasma concentrations of lunresertib with calculation of the ratio of PK parameters (e.g., Cmax and AUC) between the tablet formulation under fasted and fed state.

Secondary Outcomes

Measure	Description	Time Frame
The plasma concentrations of lunresertib monotherapy (capsule formulation) in the fasted and fed states	Assessed by the plasma concentrations of lunresertib with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female and ≥12 years-of-age at the time of informed consent.
Lansky performance status ≥50% for patients ≤16 years of age, or ECOG score of 0, 1, (or 2 for module 1) for patients >16 years of age.
Locally advanced or metastatic resistant or refractory solid tumors.
Patients <18 years of age must weigh at least 40 kg.
Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible
Next generation sequencing (NGS) report obtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarker.
CCNE1 amplification (non-equivocal) as determined by either a tumor or plasma NGS test, or FISH
FBXW7 deleterious mutations identified by either a tumor or plasma NGS test
PPP2R1A deleterious mutations identified by either a tumor or plasma NGS test
Measurable disease as per RECIST v1.1. For certain modules, patients with prostate cancer or ovarian cancer that have non-measurable disease but have elevated tumor markers (PSA or CA-125, respectively) can also be eligible
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.
Any prior radiation must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study 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.
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 lunresertib.
Uncontrolled, symptomatic brain metastases.
Uncontrolled hypertension.
Certain prior anti-cancer therapy
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.