Clinical trial NCT05167409: A Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Microsatellite Stable Metastatic Colorectal Cancer
Keywords: evorpacept (ALX148)
Cetuximab
Pembrolizumab
CRC
colorectal cancer
microsatellite stable
MSS
CD47
SIRPa
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: ALX Oncology Inc.
name: Merck Sharp & Dohme LLC
name: Eli Lilly and Company
name: Criterium, Inc.
name: Academic GI Cancer Consortium (AGICC)
First posted: 2021-12-22
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab 1.(mg/kg)
timeFrame: 4 months
measure: Objective response rate (ORR, per RECIST v1.1) (%)
timeFrame: 6 months
Secondary outcomes:
measure: Disease control rate per RECIST v1.1. (%)
timeFrame: 24 months
measure: Duration of response per RECIST v1.1. (months)
timeFrame: 24 months
measure: Progression-free survival (PFS, per RECIST v1.1) (months)
timeFrame: 48 months
measure: Overall survival (OS)
timeFrame: 48 months
measure: First cycle dose-limiting toxicities in the safety run-in stage
timeFrame: 4 months
measure: Safety and tolerability according to the NCI CTCAE v5.0
timeFrame: 48 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Brunswick
country: United States
facility: Rutgers Cancer insititute
state: New Jersey
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
Study officials:
affiliation: University of Colorado, Denver
name: Robert Lentz, MD
role: PRINCIPAL_INVESTIGATOR
References: