VX15/2503 + Immunotherapy for Head and Neck Cancer

Overseen By Nabil Saba, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Organ transplant, 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: 1

Duration: 1 day for treatment, surgery between days 17-36

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for head and neck squamous cell cancer, examining whether the monoclonal antibody VX15/2503 (also known as Pepinemab), combined with immunotherapy drugs like ipilimumab (Yervoy) and nivolumab (Opdivo), can inhibit cancer cell growth. It tests various combinations of these treatments to identify the most effective approach. Individuals with stage I-IVA head and neck cancer, who have not received prior treatment and have tumors that can be surgically removed, might be suitable candidates. Participants will receive infusions of the study drugs followed by standard surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressants or systemic corticosteroids, you may need to stop them before joining the trial. 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 VX15/2503, also known as pepinemab, has undergone safety testing in both animals and humans. Studies have examined how the treatment functions in the body and any potential harmful effects. So far, these studies suggest it is generally well-tolerated.

When combined with ipilimumab or nivolumab, early results indicate that VX15/2503 does not cause additional side effects. Ipilimumab and nivolumab are well-known cancer treatments. They are generally safe but can sometimes lead to serious side effects like inflammation. Common side effects of these drugs include tiredness and skin rashes.

Since this trial is in an early phase, it primarily focuses on testing safety. Early-phase trials typically provide limited safety evidence but aim to assess how people tolerate the treatment. This trial will help determine the safety of VX15/2503 when used alone or with these other medications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they introduce unique ways to boost the immune system against cancer cells. Unlike the standard care, which typically involves surgery, chemotherapy, and radiation, these experimental treatments combine VX15/2503 with established immunotherapy drugs like ipilimumab and nivolumab. VX15/2503 is a novel antibody that targets a specific protein on cancer cells, potentially enhancing the immune system's ability to attack the cancer. By pairing VX15/2503 with either ipilimumab or nivolumab, these treatments aim to improve the body's defense mechanisms more effectively than current options. This innovative approach could offer new hope for patients by potentially improving outcomes and reducing reliance on traditional therapies.

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

Research has shown that VX15/2503, also known as pepinemab, helps the immune system recognize and attack cancer cells by turning "cold" tumors "hot." This approach could be promising for head and neck cancers. In this trial, participants may receive VX15/2503 alone or with other treatments. When combined with nivolumab, an immune therapy, VX15/2503 enhances the body's immune response, particularly in certain head and neck cancers. Ipilimumab, another immune therapy, has proven effective in extending survival in various cancers. Participants in this trial may receive ipilimumab alone or with VX15/2503. Nivolumab alone has shown positive results in treating head and neck cancer, with fewer severe side effects than standard treatments. Together, these treatments aim to enhance the body's ability to fight cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Conor Steuer

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with stage I-IVA head and neck squamous cell carcinoma (HNSCC) that can be surgically removed. They must not have had prior HNSCC treatment, should have proper liver and kidney function, no severe allergies to monoclonal antibodies or autoimmune diseases, and agree to use contraception. Pregnant women or those on immunosuppressants are excluded.

Inclusion Criteria

My blood clotting time is normal or near normal, and if I'm on blood thinners, it's only low molecular weight heparin.

Serum creatinine ≤ 1.5 x ULN

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

I haven't had vaccines not related to cancer within 4 weeks of receiving ipilimumab.

I cannot have surgery because of other health problems.

I am on long-term immunosuppressants like cyclosporine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive VX15/2503 with or without ipilimumab or nivolumab, followed by standard of care surgery

1 day for treatment, surgery between days 17-36

1 visit (in-person) for treatment, 1 visit (in-person) for surgery

Follow-up

Participants are monitored for changes in immune profile and adverse events

4-8 weeks after surgery

Multiple visits for monitoring and sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• VX15/2503

Trial Overview The study tests VX15/2503 alone or combined with ipilimumab/nivolumab in treating early-stage HNSCC. It's a phase I trial aiming to see how well these monoclonal antibodies prevent cancer growth and spread by interfering with tumor cells.

How Is the Trial Designed?

Group I: Group E (ipilimumab) Experimental Treatment 1 Intervention

Patients receive ipilimumab IV over 90 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Group II: Group D (nivolumab) Experimental Treatment 1 Intervention

Patients receive nivolumab IV over 60 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Group III: Group C (VX15/2503, nivolumab) Experimental Treatment 2 Interventions

Patients receive VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Group IV: Group B (VX15/2503, ipilimumab) Experimental Treatment 2 Interventions

Patients receive VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Group V: Group A (VX15/2503) Experimental Treatment 1 Intervention

Patients receive VX15/2503 IV over 60 minutes on day 1. Beginning days 17-36, patients undergo standard of care surgery.

Group VI: Group F (no treatment) Active Control 1 Intervention

Patients undergo standard of care surgery.

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

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Vaccinex Inc.

Industry Sponsor

Trials

12

Recruited

740+

Published Research Related to This Trial

PD-1 inhibitors significantly improve overall survival in patients with recurrent or metastatic head and neck cancer compared to standard treatments, with a relative risk of death reduced by 40%.

Patients with human papillomavirus (HPV) positive head and neck cancer showed better response rates to PD-1/PD-L1 inhibitors than those who are HPV negative, indicating that HPV status may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. Wang, BC., Cao, RB., Li, PD., et al.[2021]

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]

PD-1 inhibitors, used for treating recurrent or metastatic squamous cell carcinoma of the head and neck, can lead to immune-mediated adverse reactions (IMARs), highlighting the importance of monitoring patients closely.

Nurses play a crucial role in mapping patients' baseline profiles and educating them about IMARs, which helps in the timely diagnosis and management of these reactions, ultimately supporting the continuation of effective PD-1 immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Inhibitors: Safety of Use and Management of Immune-Mediated Adverse Reactions in Patients With Head and Neck Cancer. Lewis, RL., Miller, KL.[2020]

In a phase Ia clinical trial involving 32 patients with advanced head and neck cancer, atezolizumab demonstrated a tolerable safety profile, with 66% of patients experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment showed promising efficacy, with 22% of patients achieving objective responses and a median overall survival of 6.0 months, indicating potential benefits regardless of HPV status or PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Colevas, AD., Bahleda, R., Braiteh, F., et al.[2022]

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]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

In a study of 174 patients with locally advanced head and neck cancer, those treated with cisplatin (CDDP) showed significantly better outcomes compared to those treated with cetuximab (C225) in terms of loco-regional failure, disease-free survival, and overall survival, with P-values indicating strong statistical significance (P<0.0001).

Even after accounting for HPV status in a subset of 62 patients, cisplatin still demonstrated superior efficacy, reinforcing the conclusion that CDDP is a more effective treatment option than C225 for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck. Riaz, N., Sherman, E., Koutcher, L., et al.[2022]

Nivolumab, a PD-1 inhibitor, has been FDA-approved for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, but treatment options remain limited for these patients.

A case study of a 46-year-old male with refractory HNSCC showed successful treatment using a combination of nivolumab and ipilimumab, suggesting potential efficacy for this combination therapy in HNSCC, similar to its success in metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. Schwab, KS., Kristiansen, G., Schild, HH., et al.[2022]

In a subgroup analysis of 33 patients with HPV-related oropharyngeal cancer, treatment with cisplatin (CDDP) showed a trend towards better locoregional control and overall survival compared to cetuximab (CTX), suggesting that CDDP may be a more effective first-line treatment for these patients.

Serious or fatal infectious complications were only observed in the CTX treatment group, indicating potential safety concerns associated with cetuximab in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer. Buglione, M., Maddalo, M., Corvò, R., et al.[2018]

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 the CheckMate 141 trial involving 361 patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck, nivolumab significantly improved patient-reported outcomes (PROs) compared to standard therapies, with no clinically meaningful deterioration in quality of life for nivolumab patients.

Nivolumab not only stabilized symptoms and functioning but also delayed the time to deterioration in quality of life measures, making it a promising new standard-of-care treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Harrington, KJ., Ferris, RL., Blumenschein, G., et al.[2022]

Citations

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The Final Results of CheckMate 651 - PubMed - NIH Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), ...

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Bristol Myers Squibb Announces Opdivo (nivolumab) Plus ... Opdivo plus Yervoy demonstrated a significantly reduced risk of symptom deterioration of 24% compared to lenvatinib or sorafenib (HR: 0.76, 95% ...

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OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Safety ... See selected safety profiles for OPDIVO® (nivolumab)+ YERVOY® (ipilimumab) in intermediate or poor risk aRCC. Please see Indications and Important Safety ...

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Squamous Cell Head and Neck (SCCHN) Cancer Treatment OPDIVO is an FDA-approved immunotherapy option to treat head and neck squamous cell carcinoma that has returned or spread after previous treatment.

9. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

067 Which Showed Continued Durable Long-Term ... With a minimum follow up of 10 years, median overall survival (OS) was 71.9 months with Opdivo plus Yervoy (95% CI: 38.2-114.4) - the longest ...