Evorpacept + Immunotherapy + Chemotherapy for Head and Neck Cancer

Not currently recruiting at 56 trial locations

Overseen By Richard J Morishige, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ALX Oncology Inc.

Must not be taking: Steroids

Disqualifiers: CNS metastases, Pneumonitis, 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: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for advanced head and neck squamous cell carcinoma, a type of cancer. Researchers aim to determine if adding evorpacept (an experimental treatment) to standard immunotherapy (pembrolizumab) and chemotherapy improves treatment outcomes. The trial includes two groups: one receives immunotherapy with chemotherapy, and the other receives evorpacept, immunotherapy, and chemotherapy. It seeks participants who have not yet received treatment for advanced head and neck cancer that has spread or cannot be surgically removed. As a Phase 2 trial, the 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 evorpacept, when combined with pembrolizumab and chemotherapy, is generally safe. Early results suggest that evorpacept is well-tolerated with various chemotherapy drugs, and no maximum safe dose has been identified. Patients typically handle the combination without serious side effects.

For pembrolizumab, studies have demonstrated its safety and effectiveness for many cancer patients, including those with head and neck cancer. No new safety issues have been reported, indicating it remains a dependable option.

Overall, previous studies have shown that the treatments in this trial are well-tolerated, offering a good safety record for those considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of evorpacept with pembrolizumab and chemotherapy for head and neck cancer because it introduces a novel approach to treatment. While standard therapies often rely on chemotherapy and immunotherapy like pembrolizumab alone, evorpacept works differently by enhancing the body's immune response against cancer cells. This unique mechanism of action potentially boosts the effectiveness of existing treatments, offering hope for improved outcomes. Furthermore, evorpacept is administered intravenously every three weeks, complementing the established schedule of current therapies, making it a promising addition to the treatment regimen.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that evorpacept, when combined with pembrolizumab and chemotherapy, may help treat head and neck squamous cell carcinoma (HNSCC). Evorpacept is a medicine that enhances the immune system's ability to identify and attack cancer cells. Early studies have found that this combination can boost the body's tumor-fighting capabilities. In this trial, some participants will receive evorpacept with pembrolizumab and chemotherapy, while others will receive pembrolizumab with chemotherapy alone. Previous studies suggest that patients who received evorpacept with pembrolizumab responded better to treatment than those who only received pembrolizumab. Additionally, earlier studies found this combination to be safe and well-tolerated, indicating that adding evorpacept could enhance the effectiveness of cancer treatments. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced head and neck squamous cell carcinoma who haven't been treated before. They should be physically able to undergo treatment (good ECOG status) and have their major organs like kidneys, liver, and bone marrow working well. People can't join if they've had certain previous cancer treatments or have brain metastases needing steroids.

Inclusion Criteria

My kidney and liver are working well.

I am able to care for myself and perform daily activities.

My head or neck cancer has not been treated and cannot be removed by surgery.

Exclusion Criteria

I have brain metastases or leptomeningeal disease and need steroids.

I have been treated with anti-PD-1 or PD-L1 therapy before.

I have not been treated with anti-CD47 or anti-SIRPα agents.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial safety lead-in to assess the safety of the treatment combination

3 weeks

1 visit (in-person)

Treatment

Participants receive evorpacept (ALX148) + pembrolizumab + chemotherapy or pembrolizumab + chemotherapy every 3 weeks

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin/Carboplatin; 5FU
• Evorpacept
• Pembrolizumab

Trial Overview The study tests Evorpacept combined with Pembrolizumab (an immunotherapy drug) and chemotherapy drugs Cisplatin/Carboplatin; 5FU in patients with advanced head and neck cancer. It's a Phase 2 trial, which means it's checking the effectiveness of this combination therapy.

How Is the Trial Designed?

Group I: evorpacept (ALX148) + pembrolizumab + Chemotherapy Experimental Treatment 3 Interventions

evorpacept (ALX148) 45 mg/kg IV, pembrolizumab 200 mg IV, and chemotherapy given every 3 weeks.

Group II: pembrolizumab + Chemotherapy Active Control 2 Interventions

pembrolizumab 200 mg IV and chemotherapy given every 3 weeks.

Who Is Running the Clinical Trial?

ALX Oncology Inc.

Lead Sponsor

Trials

9

Recruited

1,200+

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

Published Research Related to This Trial

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

The JAVELIN Head and Neck 100 study is a Phase III clinical trial investigating the effectiveness of avelumab, a PD-L1 inhibitor, combined with standard chemoradiotherapy (CRT) for high-risk, locoregionally advanced squamous cell carcinomas of the head and neck.

This study addresses a critical gap in research, as there are currently no prospective studies evaluating immune checkpoint inhibitors in the definitive treatment of nonmetastatic HNSCC, which is important for improving outcomes in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. Yu, Y., Lee, NY.[2020]

In a study of 25 patients with locally advanced squamous cell carcinoma of the head and neck who were ineligible for cisplatin, concurrent treatment with carboplatin and radiotherapy resulted in a 70% complete response rate and a median progression-free survival of 42.7 months.

The treatment was generally well-tolerated, with significant toxicities including oral mucositis (56%) and thrombocytopenia (34%), suggesting that carboplatin could be a viable alternative for patients unable to receive cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of concurrent carboplatin plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin. Hamauchi, S., Yokota, T., Onozawa, Y., et al.[2018]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04675294

Study Details | NCT04675294 | Evorpacept (ALX148) in ... This is a open-label, randomized phase 2 multi-center study of the anti-tumor efficacy of evorpacept (ALX148) + pembrolizumab and of pembrolizumab alone

2. alxoncology.com alxoncology.com/wp-content/uploads/2025/01/ALX-SITC-ASPEN04-Nov22.pdf

A Phase 2 Study of Evorpacept (ALX148) in Combination ... 498 Evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with head and neck squamous cell carcinoma. (HNSCC) and with gastric/gastroesophageal ...

3. ctv.veeva.com ctv.veeva.com/study/evorpacept-alx148-in-combination-with-pembrolizumab-in-patients-with-advanced-head-and-neck-squamo

Evorpacept (ALX148) in Combination With Pembrolizumab in ... This is a open-label, randomized phase 2 multi-center study of the anti-tumor efficacy of evorpacept (ALX148) + pembrolizumab and of pembrolizumab alone

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204521005842

Evorpacept alone and in combination with pembrolizumab ... We evaluated the safety and antitumour activity of evorpacept in patients with head and neck squamous cell carcinoma (HNSCC), non-small-cell lung cancer ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34793719/

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

6. alxoncology.com alxoncology.com/wp-content/uploads/2021/10/Lee-K-W-et-al-SITC-09Nov2021.pdf

Evorpacept (ALX148), a CD47 Myeloid Checkpoint ... • Preliminary data suggests that evorpacept can be safety combined with the multi- agent chemotherapy regimens studied with no MTD reached.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04675333

Study Details | NCT04675333 | Evorpacept (ALX148) in ... A Phase 2 Study of evorpacept (ALX148) in Combination With pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma.

8. 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.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3056

A phase I study of ALX148, a CD47 blocker, in combination ... Initial data suggests ALX148 demonstrates excellent tolerability in combination with anti cancer antibodies and standard chemotherapy.