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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Microsatellite Stable Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: Pembrolizumab; Drug: Evorpacept (ALX148)

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ruth Stone; Phone Number: 15185830095; Email: restone@criteriuminc.com
• Study Contact Backup: Name: Ash Philpott, PhD; Phone Number: 404 884 4701; Email: aphilpott@criteriuminc.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer insititute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evorpacept (ALX148) + cetuximab + 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	Drug: Cetuximab; IV QW; Other Names: Erbitux; Drug: Pembrolizumab; IV Q3W; Other Names: Keytruda; Drug: Evorpacept (ALX148); IV QW; Other Names: evorpacept

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Eli Lilly and Company; Merck Sharp & Dohme LLC; Criterium, Inc.; ALX Oncology Inc.; Academic GI Cancer Consortium (AGICC)
• Investigators: Principal Investigator: Robert Lentz, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2022
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: colorectal cancer; Pembrolizumab; Cetuximab; CRC; CD47; MSS; microsatellite stable; SIRPa; evorpacept (ALX148)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Cetuximab
• Other Study ID Numbers: 22-0110.cc; NCI-2022-02019 (Other Identifier: CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No