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

• ClinicalTrials.gov Identifier: NCT06005974
• Recruitment Status: Recruiting
• First Posted: August 23, 2023
• Last Update Posted: February 6, 2024
• Sponsor: Recursion Pharmaceuticals Inc.
• Information provided by (Responsible Party): Recursion Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: August 10, 2023
• First Posted Date: August 23, 2023
• Last Update Posted Date: February 6, 2024
• Actual Study Start Date: January 15, 2024
• Estimated Primary Completion Date: January 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2024)

• To evaluate the safety and tolerability of REC-4881 [ Time Frame: 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) [ Time Frame: 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

Original Primary Outcome Measures (submitted: August 21, 2023)

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

Current Secondary Outcome Measures (submitted: January 19, 2024)

• To characterize the PK of REC-4881 [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: August 21, 2023)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of REC-4881 in Participants With Cancers Which Have an AXIN1 or APC Mutation
• Official Title: A Phase 2, Open Label Study of REC-4881 in Participants With Unresectable Locally Advanced or Metastatic Cancer With AXIN1 or APC Mutation
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment

Condition

• AXIN1 Gene Mutation
• APC Gene Mutation
• Solid Tumor

Intervention

Drug: REC-4881

REC-4881 4mg capsules

Study Arms

• Experimental: AXIN1 Cohort
  Participants will receive REC-4881 12mg PO dosed QD
  Intervention: Drug: REC-4881
• Experimental: APC Cohort
  Participants will receive REC-4881 12mg PO dosed QD
  Intervention: Drug: REC-4881

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 21, 2023): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2027
• Estimated Primary Completion Date: January 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Recursion Pharmacueticals; 385-374-1724; clinicaltrials@recursionpharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06005974
• Other Study ID Numbers: REC-4881-221
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Recursion Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Recursion Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Recursion Pharmaceuticals Inc.
• Verification Date: February 2024