A Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer
- Conditions
- Microsatellite Stable Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT05167409
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
This Phase 2 clinical study will evaluate evorpacept (ALX148) in combination with cetuximab and pembrolizumab for refractory microsatellite stable metastatic colorectal cancer
- Detailed Description
This is an open-label, multi-center, single-arm phase II clinical trial (with safety run-in) evaluating the combination of evorpacept (ALX148), cetuximab, and pembrolizumab in patients with metastatic microsatellite stable colorectal cancer who have progressed on at least 2 lines of systemic therapy. A subset of patients will undergo study-related biopsies. There will be a safety run-in stage followed by a dose expansion stage. Patients in both stages will continue to receive study therapy until disease progression according to RECIST v1.1.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 48
To be eligible to participate in this study, an individual must meet all of the following criteria:
- Have a diagnosis of metastatic colorectal cancer previously treated with at least two lines of therapy for unresectable/metastatic disease
- Have microsatellite stable disease
- Adequate hematologic and end organ function
An individual who meets any of the following criteria will be excluded from participation in this study:
- Patients with known MSI-high status or known mismatch repair deficiency (dMMR)
- Patients in whom both mismatch repair and microsatellite stability status are unknown
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the study medications or their classes
- Left-sided (at or distal to the splenic flexure) RAS/BRAF wild-type metastatic colorectal cancer who are EGFR inhibitor naïve.
- Prior therapy with an anti-PD-1, anti-PD-L1, anti PD L2, anti-CD47, or anti-SIRPα agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Evorpacept (ALX148) + cetuximab + pembrolizumab Cetuximab Evorpacept (ALX148) + cetuximab + pembrolizumab. Evorpacept (ALX148) 15 mg/kg IV weekly, cetuximab 400 mg/m2 once then 250 mg/m2 weekly, and pembrolizumab 200 mg every 3 weeks Evorpacept (ALX148) + cetuximab + pembrolizumab Pembrolizumab Evorpacept (ALX148) + cetuximab + pembrolizumab. Evorpacept (ALX148) 15 mg/kg IV weekly, cetuximab 400 mg/m2 once then 250 mg/m2 weekly, and pembrolizumab 200 mg every 3 weeks Evorpacept (ALX148) + cetuximab + pembrolizumab Evorpacept (ALX148) Evorpacept (ALX148) + cetuximab + pembrolizumab. Evorpacept (ALX148) 15 mg/kg IV weekly, cetuximab 400 mg/m2 once then 250 mg/m2 weekly, and pembrolizumab 200 mg every 3 weeks
- Primary Outcome Measures
Name Time Method Recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab 1.(mg/kg) 4 months To determine the recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab
Objective response rate (ORR, per RECIST v1.1) (%) 6 months To determine the objective response rate (ORR), defined as partial response or complete response, with evorpacept (ALX148), cetuximab, and pembrolizumab using RECIST v1.1 in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) who have progressed on at least two lines of standard therapy
- Secondary Outcome Measures
Name Time Method Disease control rate per RECIST v1.1. (%) 24 months To determine the disease-control rate (DCR), defined as stable disease, partial response, or complete response with evorpacept (ALX148), cetuximab, and pembrolizumab using RECIST v1.1
Duration of response per RECIST v1.1. (months) 24 months To determine the duration of response (DOR) with evorpacept (ALX148), cetuximab, and pembrolizumab, defined as the time from response (partial or complete) to progression
Progression-free survival (PFS, per RECIST v1.1) (months) 48 months To determine the progression-free survival (PFS) with evorpacept (ALX148), cetuximab, and pembrolizumab, defined as the time from enrollment to the first observation of progression using RECIST v1.1 or death from any cause
First cycle dose-limiting toxicities in the safety run-in stage 4 months To determine the first cycle dose-limiting toxicities (DLT) of evorpacept (ALX148), cetuximab, and pembrolizumab in stage 1
Overall survival (OS) 48 months To determine the overall survival (OS) with evorpacept (ALX148), cetuximab, and pembrolizumab, defined as the time from enrollment to death from any cause
Safety and tolerability according to the NCI CTCAE v5.0 48 months To evaluate the safety and tolerability of evorpacept (ALX148), cetuximab, and pembrolizumab, defined and graded according to the NCI CTCAE v5.0
Trial Locations
- Locations (4)
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Rutgers Cancer insititute
🇺🇸New Brunswick, New Jersey, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States