A Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This Phase 2 clinical study will evaluate evorpacept (ALX148) in combination with cetuximab and pembrolizumab for refractory microsatellite stable metastatic colorectal cancer

Detailed Description
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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.

Official Title
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A Phase II Study (With Safety run-in) of Evorpacept (ALX148) in Combination With Cetuximab and Pembrolizumab in Patients With Refractory Microsatellite Stable Metastatic Colorectal Cancer

Conditions
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Microsatellite Stable Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Evorpacept (ALX148)
* Drug: Cetuximab
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evorpacept (ALX148) + cetuximab + pembrolizumab<br>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 | Drug: Evorpacept (ALX148)<br>* IV QW<br>* Other names: evorpacept;Drug: Cetuximab<br>* IV QW<br>* Other names: Erbitux;Drug: Pembrolizumab<br>* IV Q3W<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab 1.(mg/kg) | To determine the recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab | 4 months | 
| Objective response rate (ORR, per RECIST v1.1) (%) | 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 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate per RECIST v1.1. (%) | 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 | 24 months | 
| Duration of response per RECIST v1.1. (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 | 24 months | 
| Progression-free survival (PFS, per RECIST v1.1) (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 | 48 months | 
| Overall survival (OS) | To determine the overall survival (OS) with evorpacept (ALX148), cetuximab, and pembrolizumab, defined as the time from enrollment to death from any cause | 48 months | 
| First cycle dose-limiting toxicities in the safety run-in stage | To determine the first cycle dose-limiting toxicities (DLT) of evorpacept (ALX148), cetuximab, and pembrolizumab in stage 1 | 4 months | 
| Safety and tolerability according to the NCI CTCAE v5.0 | To evaluate the safety and tolerability of evorpacept (ALX148), cetuximab, and pembrolizumab, defined and graded according to the NCI CTCAE v5.0 | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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evorpacept (ALX148), Cetuximab, Pembrolizumab, CRC, colorectal cancer, microsatellite stable, MSS, CD47, SIRPa