Evorpacept + Pembrolizumab for Head and Neck Cancer

Not currently recruiting at 69 trial locations

Overseen By Chaitali Nangia, MD

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: 2

Duration: Ongoing every 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, evorpacept (a CD47/SIRPa-blocking agent) and pembrolizumab, for individuals with advanced head and neck cancer. The main goal is to determine if this combination can effectively treat squamous cell carcinoma, a type of skin cancer in the head and neck area, particularly for those whose cancer has spread or cannot be surgically removed. The trial includes two groups: one receiving only pembrolizumab and another receiving both evorpacept and pembrolizumab. It seeks participants whose cancer is PD-L1 positive and who have not received any prior treatments for their advanced disease. 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 whether 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 the combination of evorpacept and pembrolizumab is generally well-tolerated by patients. Safety findings indicate that this combination can be used in patients with advanced solid tumors without major safety concerns. In previous studies, patients did not experience severe side effects at the doses tested.

The FDA has approved pembrolizumab as a treatment for various cancers, including head and neck cancer, confirming its safety when used alone.

Overall, evidence supports the safety of using both evorpacept and pembrolizumab together, making this combination a promising option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about evorpacept combined with pembrolizumab for head and neck cancer because it introduces a novel approach by targeting the CD47-SIRPα pathway, which is a new mechanism of action compared to traditional treatments like chemotherapy or standalone immunotherapies. Most treatments for head and neck cancer, like pembrolizumab alone or chemotherapy, focus on either directly attacking cancer cells or enhancing the immune response. However, evorpacept adds an innovative layer by potentially improving immune system recognition of cancer cells, making it more effective when used with pembrolizumab. This combination could enhance the body's ability to fight cancer more effectively, offering hope for better outcomes.

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

Research has shown that using evorpacept with pembrolizumab may help treat advanced head and neck cancer. In this trial, one group of participants will receive the combination of evorpacept and pembrolizumab. Earlier studies found that 40% of patients with advanced solid tumors, including head and neck cancer, experienced tumor shrinkage or disappearance with this combination treatment. On average, patients lived 4.6 months without their cancer worsening. These results suggest that evorpacept, when combined with pembrolizumab, could improve outcomes for people with this type of cancer. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced head and neck squamous cell carcinoma that hasn't spread too far, is PD-L1 positive, and who haven't had systemic therapy before. They need to be relatively healthy in terms of bone marrow, kidney, liver function, and overall activity level.

Inclusion Criteria

My head/neck cancer is advanced, hasn't been treated yet, and tests positive for PD-L1.

My kidney and liver are working well.

My bone marrow is working well.

Exclusion Criteria

I need steroids for my brain or spinal cord cancer symptoms.

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

I have had or currently have lung inflammation treated with steroids.

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 cohort to assess the safety of evorpacept (ALX148) + pembrolizumab

3 weeks

1 visit (in-person)

Treatment

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

Ongoing every 3 weeks

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Evorpacept
• Pembrolizumab

Trial Overview The study tests Evorpacept (ALX148) combined with Pembrolizumab on patients. It's a Phase 2 trial which means they're looking at how effective this combo is against head and neck cancer and gathering more info on safety.

How Is the Trial Designed?

Group I: evorpacept (ALX148) + pembrolizumab Experimental Treatment 2 Interventions

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

Group II: pembrolizumab Active Control 1 Intervention

pembrolizumab 200 mg IV 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

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]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[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 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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04675333

Study Details | NCT04675333 | Evorpacept (ALX148) in ... This is a open-label, randomized phase 2 multi-center study of the anti-tumor efficacy of evorpacept (ALX148) + pembrolizumab + 5FU + platinum and of ...

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. alxoncology.com alxoncology.com/wp-content/uploads/2021/11/ALX-SITC-ASPEN-03-Nov21.pdf

ASPEN-03 platinum-based therapy (n=10) were treated with evorpacept + pembrolizumab and experienced a 40% ORR and 4.6 months median PFS, comparing favorably with ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04675294/

Clinical Trial: NCT04675294 A Phase 2 Study of Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma.

6. 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.

7. 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.