Evorpacept + Cetuximab + Pembrolizumab for Colorectal Cancer

Not currently recruiting at 7 trial locations

Overseen By Ash Philpott, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: MSI-high, dMMR, hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three treatments—evorpacept (a CD47/SIRPa-blocking agent), cetuximab, and pembrolizumab—to determine their effectiveness against a challenging type of colorectal cancer that has spread and lacks certain genetic features (microsatellite stable). The goal is to assess whether these drugs can help when other treatments have failed. The trial seeks participants who have already received at least two types of treatment for their metastatic colorectal cancer and have microsatellite stable disease. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining evorpacept, cetuximab, and pembrolizumab is generally safe for patients with advanced cancers. In earlier studies, most patients did not experience severe side effects. The side effects that did occur were manageable, with common ones being tiredness, nausea, and skin rash, which are typical for cancer treatments.

Evorpacept, when combined with pembrolizumab, has undergone safety testing in various cancer types. The results support its use, indicating that most side effects were mild to moderate. Cetuximab and pembrolizumab are already approved for other cancers, which adds confidence in their safety. Patients should always consult a healthcare provider to understand the potential risks and benefits for their specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Evorpacept, Cetuximab, and Pembrolizumab for colorectal cancer because Evorpacept introduces a novel mechanism of action. While Cetuximab and Pembrolizumab are already used to target specific cancer pathways, Evorpacept enhances the immune system's ability to destroy cancer cells by blocking a protein called CD47, which is often used by cancer cells to hide from the immune system. This combination aims to boost the effectiveness of the immune response against cancer more than current treatments do, offering new hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research shows that combining three drugs—evorpacept, cetuximab, and pembrolizumab—may help treat a difficult-to-treat type of metastatic colorectal cancer. This trial will test this specific combination. Previous studies found that cetuximab alone extended survival for patients with this cancer. Evorpacept and pembrolizumab together have shown safety in patients with advanced cancers. Early results from studies on this specific combination suggest improved effectiveness. Researchers are testing this combination because each drug targets cancer cells differently, potentially leading to better patient outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Robert W. Lentz

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults with metastatic colorectal cancer that's microsatellite stable and has resisted at least two previous treatments. They must have good blood counts and organ function. It's not for those with certain genetic features (MSI-high or dMMR), severe allergies to study drugs, prior treatment with similar immune-targeting drugs, or specific types of untreated left-sided colorectal cancer.

Inclusion Criteria

My blood and organs are functioning well.

I have colorectal cancer that has spread and received at least two treatments.

My cancer is microsatellite stable.

Exclusion Criteria

My cancer is MSI-high or has mismatch repair deficiency.

You have had severe allergic reactions to any of the study medications or similar medications in the past.

I don't know my cancer's mismatch repair or microsatellite status.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial phase to determine first cycle dose-limiting toxicities and recommended dose of evorpacept (ALX148) in combination with cetuximab and pembrolizumab

4 months

Treatment

Participants receive evorpacept (ALX148), cetuximab, and pembrolizumab until disease progression

48 months

Follow-up

Participants are monitored for overall survival and progression-free survival

48 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Evorpacept (ALX148)
• Pembrolizumab

Trial Overview The study tests Evorpacept (ALX148) combined with Cetuximab and Pembrolizumab in patients whose metastatic colorectal cancer hasn't responded to other treatments. This Phase 2 trial aims to see how well these medications work together against this type of cancer.

How Is the Trial Designed?

Group I: Evorpacept (ALX148) + cetuximab + pembrolizumab Experimental Treatment 3 Interventions

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

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Criterium, Inc.

Industry Sponsor

Trials

18

Recruited

730+

Academic GI Cancer Consortium (AGICC)

Collaborator

Trials

3

Recruited

210+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

ALX Oncology Inc.

Industry Sponsor

Trials

9

Recruited

1,200+

Published Research Related to This Trial

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

Cetuximab and panitumumab are effective treatments for colorectal cancer, showing clinical activity as anti-EGFR monoclonal antibodies, and are generally well tolerated by patients.

While these medications have fewer severe adverse events compared to traditional cytotoxic agents, they can still cause issues like infusion reactions, skin toxicity, lung toxicity, and low magnesium levels, which need to be managed promptly to avoid treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-epidermal growth factor receptor monoclonal antibodies induced adverse events]. Tsuji, Y., Kogawa, T., Abe, M.[2018]

In a study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3530

Results of a phase 2 study of evorpacept (E, ALX148), ... A phase 2 study of evorpacept (E, ALX148), cetuximab (C), and pembrolizumab (P) in patients with refractory microsatellite stable metastatic colorectal cancer ...

2. alxoncology.com alxoncology.com/wp-content/uploads/2024/05/Results-of-a-phase-2-study-of-evorpacept-cetuximab-and-pembrolizumab-in-patients-with-refractory-microsatellite-stable-metastatic-colorectal-cancer-May24a.pdf

Results-of-a-phase-2-study-of-evorpacept-cetuximab-and- ... Results of a phase 2 study of evorpacept (E, ALX148), cetuximab (C), and pembrolizumab (P) in patients with refractory.

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00584-2/abstract

Evorpacept alone and in combination with pembrolizumab ... The safety findings support the use of evorpacept in combination with pembrolizumab or trastuzumab for patients with advanced solid tumours.

4. withpower.com withpower.com/trial/evorpacept-cetuximab-pembrolizumab-for-colorectal-cancer-6f4a6

Evorpacept + Cetuximab + Pembrolizumab for Colorectal ... Cetuximab, one of the drugs in the combination, has been shown to improve survival and response rates in patients with metastatic colorectal cancer, especially ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT389232

A phase II study (with safety run-in) of evorpacept (ALX148) ... Trial in progress: A phase II study (with safety run-in) of evorpacept (ALX148), cetuximab, and pembrolizumab in patients with refractory microsatellite-stable ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05167409?tab=history&a=15

Record History | ver. 15: 2024-08-21 | NCT05167409 A Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer. ClinicalTrials.gov ID ...