Pepinemab + Pembrolizumab for Head and Neck Cancer

(KEYNOTE-B84 Trial)

No longer recruiting at 15 trial locations

Overseen By Carla Kipple

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vaccinex Inc.

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Nasopharynx SCC, CNS metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 27

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment pairing for individuals with recurrent or metastatic head and neck cancer. Researchers aim to determine if combining pepinemab (an experimental treatment) with pembrolizumab (an immunotherapy drug) is safe and tolerable as a first-line treatment. Potential participants include those with head and neck cancer not treatable with local therapies and diagnosed with squamous cell carcinoma that recurs or has spread. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require immunosuppressive therapy or have received certain treatments recently. It's best to discuss your specific medications with the trial team.

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

Research has shown that combining pepinemab and pembrolizumab is promising in terms of safety for patients with head and neck cancer. Studies have found this combination to be safe and well-tolerated as an initial treatment for those with advanced or metastatic head and neck squamous cell carcinoma.

Patients receiving this treatment have not reported any unexpected severe side effects, indicating that it is generally manageable, though some may require dose adjustments. The results so far are encouraging and suggest this could be a viable option for patients seeking new treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pepinemab and pembrolizumab for head and neck cancer because it offers a novel approach compared to existing treatments like surgery, radiation, and chemotherapy. While pembrolizumab is already known as an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, pepinemab brings in a unique mechanism by blocking a protein called SEMA4D, potentially enhancing the immune response further. This combination aims to create a more robust immune attack on cancer cells, which could lead to improved outcomes for patients.

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

Research has shown that combining pepinemab and pembrolizumab might effectively treat head and neck cancer. In this trial, participants will receive this combination, as studies indicate that pepinemab enhances the effects of pembrolizumab, an immune therapy, by strengthening the body's immune response against tumors. This combination has proven safe and well-tolerated in patients with advanced head and neck cancer. Early findings suggest that pepinemab helps create structures in tumors that support a stronger immune attack. These initial results are promising for those considering this treatment option. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who have not been cured by existing treatments. Participants must be over 18, have a life expectancy of at least 12 weeks, and show measurable disease progression. They need proper liver, blood, and kidney function; HIV-positive patients must meet specific criteria. Pregnant women can't join, and those able to conceive must use effective contraception.

Inclusion Criteria

My kidney function is within the normal range.

Subjects or their legal representative must be able to provide written informed consent to participate in the trial prior to the performance of any study-specific procedures

I am HIV positive, on treatment, and my HIV is well-controlled.

Exclusion Criteria

Subjects with prior allogenic transplants

Subjects who are hepatitis B surface antigen positive

Subjects with any intercurrent medical condition where the known risks of participation in the trial outweigh any potential benefits

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Evaluate the safety and tolerability of pepinemab in combination with pembrolizumab and determine a recommended Phase 2 dose (RP2D)

9 weeks

Baseline, week 9

Dose Expansion

Evaluate objective response rate (ORR) of the combination of pepinemab/pembrolizumab in immunotherapy naïve patients

1 year

Every 6 weeks through year 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 12 weeks after safety follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Pepinemab

Trial Overview

The trial is testing the combination of two drugs: pepinemab and pembrolizumab as a first-line treatment for R/M HNSCC. The goal is to assess safety, tolerability, and determine the optimal dose for Phase 2 trials.

How Is the Trial Designed?

Group I: pepinemab + pembrolizumab Experimental Treatment 1 Intervention

Pepinemab will be administered at 20 mg/kg (with possible dose modifications to 15 mg/kg or 10 mg/kg, if the initial 20 mg/kg dose of pepinemab is determined not to be well tolerated) in combination with a fixed dose of 200 mg pembrolizumab, administered in separate IV infusions, Q3W.

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Vaccinex Inc.

Lead Sponsor

Trials

12

Recruited

740+

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

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04815720

Study Details | NCT04815720 | Pepinemab in Combination ...

The purpose of the study is to evaluate the safety and tolerability of pepinemab in combination with pembrolizumab as first-line treatment and determine a ...

2.

ir.vaccinex.com

ir.vaccinex.com/news-releases/news-release-details/vaccinex-report-promising-new-clinical-results-neoadjuvant

Vaccinex to Report Promising New Clinical Results of ...

New data presented at ASCO will characterize the mechanisms of neoadjuvant treatment with pepinemab in patients with resectable head and neck cancer (HNSCC).

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2603

Correlative and spatial biomarker analysis of a phase 1/2b ...

Correlative and spatial biomarker analysis of a phase 1/2b study to evaluate pepinemab in combination with pembrolizumab for first-line ...

4.

ir.vaccinex.com

ir.vaccinex.com/news-releases/news-release-details/vaccinex-reports-improved-immunity-correlating-clinical-benefit

Pepinemab appears to enhance clinical activity of immune ...

Pepinemab appears to enhance clinical activity of immune checkpoint inhibitors via induction of mature tertiary lymphoid structures in tumors.

5.

onclive.com

onclive.com/view/pembrolizumab-pepinemab-combo-safe-well-tolerated-in-advanced-recurrent-or-metastatic-hnscc

Pembrolizumab/Pepinemab Combo Safe, Well Tolerated in ...

The combination of pembrolizumab and pepinemab showcased encouraging safety and tolerability when given as first-line treatment in patients ...

6.

ir.vaccinex.com

ir.vaccinex.com/node/10606/pdf

Vaccinex to Report Promising New Clinical ...

corresponding with improved survival benefit in patients with melanoma and head and neck cancer at the 2025 Annual Meeting of American. Association for Cancer ...

7.

nasdaq.com

nasdaq.com/articles/vaccinex-inc-announces-promising-data-pepinemab-neoadjuvant-immunotherapy-metastatic

Vaccinex, Inc. Announces Promising Data on Pepinemab ...

Neoadjuvant pepinemab treatment shows potential to enhance immune response and improve survival in metastatic melanoma and head and neck cancer.