NCT05985954

Open-label Phase 1b Study of Ulixertinib and Cetuximab or Ulixertinib in Combination With Cetuximab and Encorafenib in Patients With Unresectable or Metastatic Colorectal Cancer Who Have Previously Received EGFR or BRAF-directed Therapy

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To find the recommended dose of ulixertinib that can be given in combination with cetuximab and/or encorafenib to patients with unresectable/metastatic CRC and who have received EGFR or BRAF-directed therapy in the past.

Detailed description

Primary Objective: The primary objective is to establish the safety, maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of small molecule inhibitor ulixertinib when combined with EGFR inhibitor cetuximab. Primary Endpoints: 1. MTD based on number of dose-limiting toxicities (DLTs) 2. RP2D based on MTD Secondary Objectives: 1. To evaluate the safety and efficacy of ulixertinib in combination with cetuximab +/- encorafenib 2. Safety profile per CTCAE v5.0, including term, incidence, severity, and duration of AEs 3. Overall response rate (ORR) and Duration of response (DOR), according to RECIST v1.1 4. Median progression free survival (PFS), according to RECIST v1.1 and median overall survival (OS) Exploratory Objectives: The exploratory objective is to evaluate the effects of ulixertinib plus cetuximab on pharmacodynamic markers. Exploratory Endpoint(s): 1. Correlative studies will be performed using blood tissue specimens from participants to assess blood- and tissue-based biomarkers, gene alterations, immunologic markers and pharmacodynamic markers from study treatment. 2. To evaluate the effects of ulixertinib on pharmacodynamic markers: ctDNA tissue biopsies, and/or blood to assess biomarkers. Assays include, but are not limited to, Reverse Phase Protein Arrays (RPPA) to assess protein levels and Nanostring and/or RNA-exome to assess mRNA expression in tissue pre- and post-ulixertinib treatment.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Cetuximab	Given by IV (vein)
DRUG	Ulixertinib	Given by PO
DRUG	Encorafenib	Given by PO

Timeline

• Start date: 2024-01-18
• Primary completion: 2028-03-28
• Completion: 2028-03-28
• First posted: 2023-08-14
• Last updated: 2026-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study