Back to resultsA Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer
Primary Purpose
Microsatellite Stable Metastatic Colorectal Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Evorpacept (ALX148)
Cetuximab
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Microsatellite Stable Metastatic Colorectal Cancer focused on measuring evorpacept (ALX148), Cetuximab, Pembrolizumab, CRC, colorectal cancer, microsatellite stable, MSS, CD47, SIRPa
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)
Sites / Locations
- University of Arizona Cancer Center
- University of Colorado Cancer Center
- Rutgers Cancer insititute
- Inova Schar Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Evorpacept (ALX148) + cetuximab + pembrolizumab
Arm Description
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
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
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
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
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
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
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
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
Full Information
NCT ID
NCT05167409
First Posted
September 27, 2021
Last Updated
September 12, 2023
Sponsor
University of Colorado, Denver
Collaborators
ALX Oncology Inc., Merck Sharp & Dohme LLC, Eli Lilly and Company, Criterium, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05167409
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 14, 2022 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
March 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
ALX Oncology Inc., Merck Sharp & Dohme LLC, Eli Lilly and Company, Criterium, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Microsatellite Stable Metastatic Colorectal Cancer
Keywords
evorpacept (ALX148), Cetuximab, Pembrolizumab, CRC, colorectal cancer, microsatellite stable, MSS, CD47, SIRPa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Evorpacept (ALX148) + cetuximab + pembrolizumab
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Evorpacept (ALX148)
Other Intervention Name(s)
evorpacept
Intervention Description
IV QW
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
IV QW
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
IV Q3W
Primary Outcome Measure Information:
Title
Recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab 1.(mg/kg)
Description
To determine the recommended dose (RD) of evorpacept (ALX148) in combination with cetuximab and pembrolizumab
Time Frame
4 months
Title
Objective response rate (ORR, per RECIST v1.1) (%)
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Disease control rate per RECIST v1.1. (%)
Description
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
Time Frame
24 months
Title
Duration of response per RECIST v1.1. (months)
Description
To determine the duration of response (DOR) with evorpacept (ALX148), cetuximab, and pembrolizumab, defined as the time from response (partial or complete) to progression
Time Frame
24 months
Title
Progression-free survival (PFS, per RECIST v1.1) (months)
Description
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
Time Frame
48 months
Title
Overall survival (OS)
Description
To determine the overall survival (OS) with evorpacept (ALX148), cetuximab, and pembrolizumab, defined as the time from enrollment to death from any cause
Time Frame
48 months
Title
First cycle dose-limiting toxicities in the safety run-in stage
Description
To determine the first cycle dose-limiting toxicities (DLT) of evorpacept (ALX148), cetuximab, and pembrolizumab in stage 1
Time Frame
4 months
Title
Safety and tolerability according to the NCI CTCAE v5.0
Description
To evaluate the safety and tolerability of evorpacept (ALX148), cetuximab, and pembrolizumab, defined and graded according to the NCI CTCAE v5.0
Time Frame
48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Lentz, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rutgers Cancer insititute
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Inova Schar Cancer Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer
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