A Study of REC-4881 in Participants With Cancers Which Have an AXIN1 or APC Mutation

Study Overview
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Brief Summary
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This is a multi-center, open-label study to investigate the safety, efficacy and pharmacokinetics of REC-4881 (12 mg PO daily doses) for the treatment of participants with unresectable locally advanced or metastatic solid tumors with AXIN1 or APC mutation.

Detailed Description
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Approximately 60 individuals will be enrolled in this open-label Phase 2 study, allocated 1:1 between the 2 cohorts - AXIN1 mutation or APC mutation. The purpose of the study is to investigate the safety, efficacy, and pharmacokinetics of REC-4881 for the treatment of participants with unresectable locally advanced or metastatic solid tumors with either mutation. Participants will receive treatment with REC-4881 (12mg PO daily) for up to 2 years.

Official Title
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A Phase 2, Open Label Study of REC-4881 in Participants With Unresectable Locally Advanced or Metastatic Cancer With AXIN1 or APC Mutation

Conditions
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AXIN1 Gene Mutation, APC Gene Mutation, Solid Tumor

Intervention / Treatment
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* Drug: REC-4881


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older with histologically-confirmed unresectable, locally advanced, or metastatic solid tumor with AXIN1 or APC mutation. If a participant has colorectal cancer, then they must be RAS / RAF wild type to enroll into the APC mutant cohort Have experienced progressive disease, relapsed disease, or be intolerant to at least one established standard systemic anti-cancer treatment, or in the opinion of the Investigator have been considered ineligible for standard therapy Measurable disease at baseline per RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Exclusion Criteria: Received treatment with another mitogen-activated protein kinase (MEK) inhibitor within two months of first dose of REC-4881 Left ventricular ejection fraction (LVEF) <50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are allocated to two groups, AXIN1 mutation or APC mutation, in parallel for the duration of the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AXIN1 Cohort<br>Participants will receive REC-4881 12mg PO dosed QD | Drug: REC-4881<br>* REC-4881 4mg capsules<br>|
| Experimental: APC Cohort<br>Participants will receive REC-4881 12mg PO dosed QD | Drug: REC-4881<br>* REC-4881 4mg capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (AEs) | Safety and tolerability | Assessed from time of ICF signature through up to 24 months of study treatment | 
| Evaluate the Objective Response Rate (ORR) of REC-4881 using RECIST 1.1 criteria | Efficacy | Tumor imaging and RECIST assessments will occur at screening and at varying intervals through study completion, an average of 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum (peak) plasma drug concentration (Cmax) | Efficacy | Assessed pre-dose and at multiple timepoints up to 24 months | 
| Time to reach maximum (peak) plasma concentration (Tmax) | Efficacy | Assessed pre-dose and at multiple timepoints up to 24 months | 
| Area under the plasma concentration-time curve (AUC) | Efficacy | Assessed pre-dose and at multiple timepoints up to 24 months | 
| Duration of Response (DOR) and Time to Response (TTR) | Efficacy | Tumor imaging and RECIST assessments will occur at screening and at varying intervals through study completion, an average of 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AXIN1, APC, Locally advanced or metastatic, Solid tumor