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

Phase 2

Active, not recruiting

• Conditions: AXIN1 Gene Mutation; APC Gene Mutation; Solid Tumor
• Interventions: Drug: REC-4881

• Registration Number: NCT06005974
• Lead Sponsor: Recursion Pharmaceuticals Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-08-10
• Study First Submitted QC: 2023-08-21
• Study First Posted: 2023-08-23
• Study Start: 2024-01-15
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-29
• Primary Completion: 2027-01
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. 55 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
2. 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
3. Measurable disease at baseline per RECIST 1.1 criteria
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Read More

Exclusion Criteria

1. Received treatment with another mitogen-activated protein kinase (MEK) inhibitor within two months of first dose of REC-4881
2. Left ventricular ejection fraction (LVEF) <50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
APC Cohort	REC-4881	Participants will receive REC-4881 12mg PO dosed QD
AXIN1 Cohort	REC-4881	Participants will receive REC-4881 12mg PO dosed QD

Primary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of REC-4881	Assessed from time of ICF signature through up to 24 months of study treatment	Assessment of dose limiting toxicities \[(DLTs) Safety Assessment Period only\]; Treatment emergent adverse events; Serious adverse events; Treatment discontinuation and dose modification due to toxicity
To evaluate the preliminary anti-tumor activity of REC-4881 as measured by Objective Response Rate (ORR)	Tumor imaging and RECIST assessments will occur at screening and at varying intervals through study completion, a maximum of 24 months	ORR according to standard RECIST 1.1 criteria

Secondary Outcome Measures

Name	Time	Method
To characterize the PK of REC-4881	Assessed pre-dose and at multiple timepoints up to 24 months	Plasma PK parameters, as appropriate, including but not limited to Cmax, Tmax, Ctrough and AUC
To assess the anti-tumor activity of REC-4881 as measured by to other efficacy endpoints	Tumor imaging and RECIST assessments will occur at screening and at varying intervals through study completion, an average of 24 months	DCR according to standard RECIST 1.1; Duration of response (DOR), Duration of SD, and TTR

Trial Locations

Locations (13)

Sharp Memorial Hospital; 🇺🇸 San Diego, California, United States

Sansum Clinic; 🇺🇸 Santa Barbara, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Denver, Colorado, United States

Medical Oncology Hematology Consultants; 🇺🇸 Newark, Delaware, United States

Mission Cancer And Blood; 🇺🇸 Des Moines, Iowa, United States

American Oncology Partners of Maryland, PA; 🇺🇸 Bethesda, Maryland, United States

Saint Luke's Hospital; 🇺🇸 Kansas City, Missouri, United States

Hunterdon Hematology Oncology; 🇺🇸 Hillsborough, New Jersey, United States

Mary Crowley Cancer Research Centers; 🇺🇸 Dallas, Texas, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Eastern Connecticut Hematology & Oncology Associates; 🇺🇸 Norwich, Connecticut, United States

Cancer Specialists of North Florida; 🇺🇸 Fleming Island, Florida, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States