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

Sponsor

Criterium, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05167409

Collaborator

ALX Oncology Inc. (Industry), Merck Sharp & Dohme LLC (Industry), Eli Lilly and Company (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

26.7

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Microsatellite Stable Metastatic Colorectal Cancer	Drug: ALX148 Drug: Cetuximab Drug: Pembrolizumab	Phase 2

Detailed Description

This is an open-label, multi-center, single-arm phase II clinical trial (with safety run-in) evaluating the combination of 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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALX148 + cetuximab + pembrolizumab ALX148 + cetuximab + pembrolizumab. ALX148 15 mg/kg IV weekly, cetuximab 400 mg/m2 once then 250 mg/m2 weekly, and pembrolizumab 200 mg every 3 weeks	Drug: ALX148 IV QW Other Names: evorpacept Drug: Cetuximab IV QW Other Names: Erbitux Drug: Pembrolizumab IV Q3W Other Names: Keytruda

Arm

Intervention/Treatment

Experimental: ALX148 + cetuximab + pembrolizumab

ALX148 + cetuximab + pembrolizumab. ALX148 15 mg/kg IV weekly, cetuximab 400 mg/m2 once then 250 mg/m2 weekly, and pembrolizumab 200 mg every 3 weeks

Drug: ALX148

IV QW

Other Names:

evorpacept

Drug: Cetuximab

IV QW

Other Names:

Erbitux

Drug: Pembrolizumab

IV Q3W

Other Names:

Keytruda

Outcome Measures

Primary Outcome Measures

Recommended dose (RD) of ALX148 in combination with cetuximab and pembrolizumab 1.(mg/kg) [4 months]
To determine the recommended dose (RD) of 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 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. (%) [24 months]
To determine the disease-control rate (DCR), defined as stable disease, partial response, or complete response with 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 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 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) [48 months]
To determine the overall survival (OS) with 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 [4 months]
To determine the first cycle dose-limiting toxicities (DLT) of ALX148, cetuximab, and pembrolizumab in stage 1
Safety and tolerability according to the NCI CTCAE v5.0 [48 months]
To evaluate the safety and tolerability of ALX148, cetuximab, and pembrolizumab, defined and graded according to the NCI CTCAE v5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
2	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
3	Rutgers Cancer insititute	New Brunswick	New Jersey	United States	08903