VX15/2503 + Immunotherapy for Head and Neck Cancer

Overseen by Conor Steuer

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Emory University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Organ transplant, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase I trial studies how well anti-semaphorin 4D (SEMA4D) monoclonal antibody VX15/2503 (VX15/2503) with or without ipilimumab and/or nivolumab work in treating patients with stage I-IVA head and neck squamous cell cancer. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.

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.

What data supports the effectiveness of the drug combination VX15/2503, Ipilimumab, Yervoy, Nivolumab, and Opdivo for head and neck cancer?

Nivolumab has been shown to significantly improve survival in patients with recurrent or metastatic head and neck cancer compared to standard therapies. Additionally, the combination of nivolumab and ipilimumab has been effective in treating metastatic melanoma, suggesting potential benefits for head and neck cancer as well. ^{1 2 3 4 5}

Is the combination of VX15/2503 and immunotherapy safe for humans?

The safety of PD-1/PD-L1 inhibitors, which are similar to some of the drugs in your trial, has been studied in head and neck cancer, showing an acceptable safety profile with some risk of immune-related side effects. However, specific safety data for VX15/2503 in combination with these therapies is not provided in the available research. ^{4 6 7 8 9}

What makes the drug VX15/2503 + Immunotherapy unique for head and neck cancer?

The combination of VX15/2503 with immunotherapy drugs like Ipilimumab and Nivolumab is unique because it targets the immune system to fight head and neck cancer, which is different from traditional chemotherapy. This approach uses immune checkpoint inhibitors to help the body's immune system recognize and attack cancer cells, offering a novel treatment option for patients with limited alternatives. ^{1 4 5 10 11}

Research Team

Conor Steuer

Principal Investigator

Emory University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Ipilimumab (Checkpoint Inhibitor)
• Nivolumab (Checkpoint Inhibitor)
• VX15/2503 (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

Vaccinex Inc.

Industry Sponsor

Trials

12

Recruited

740+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. [2019]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck. [2022]

4. England 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. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

7. United States 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]

9. United States 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. [2021]

10. England 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. [2020]

11. United States 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. [2018]