VX15/2503 + Immunotherapy for Skin Cancer

Overseen By Michael Lowe, MD, MA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Organ transplant, Autoimmune diseases, others

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

Compensation: Varies

Number of Visits: 92

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VX15/2503 (also known as Pepinemab), along with other medications like ipilimumab and nivolumab, for individuals with stage IIIB-D melanoma that can be surgically removed. The goal is to determine if these treatments can prevent the cancer from growing and spreading. Participants will receive different combinations of these drugs before undergoing surgery. This trial targets individuals diagnosed with stage IIIB-D melanoma who have not yet received certain types of immunotherapy. 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 protocol 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.

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

Research shows that the drug VX15/2503, also known as pepinemab, is being tested with other drugs, nivolumab and/or ipilimumab, to assess its safety in treating melanoma, a type of skin cancer. Early results from other studies suggest that pepinemab, when combined with these drugs, is usually well-tolerated by patients.

Nivolumab can cause serious side effects in some people, such as diarrhea and pneumonia, though these are rare. Ipilimumab also has side effects, but they can usually be managed with medical care.

This trial is in an early stage, so researchers are still evaluating the treatment's safety for participants. While the treatment combinations are experimental, these drugs have been used in other studies with some success. The aim is to determine if they can safely help stop cancer from growing and spreading.

Before joining a trial, discussing possible side effects with healthcare providers is important to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VX15/2503 (pepinemab) alongside immunotherapy for skin cancer because it introduces a novel mechanism of action. Unlike most treatments that focus on inhibiting certain pathways, VX15/2503 targets the SEMA4D pathway, potentially enhancing the immune system's ability to attack cancer cells. Combining this with established immunotherapies like nivolumab and ipilimumab, which boost the immune response, could offer a more robust strategy against skin cancer. This approach could lead to more effective and quicker outcomes than traditional treatments such as chemotherapy or radiation.

What evidence suggests that this trial's treatments could be effective for skin cancer?

Research shows that VX15/2503, also known as pepinemab, targets a protein called SEMA4D, which can help stop cancer cells from growing and spreading. Participants in this trial may receive VX15/2503 with nivolumab, ipilimumab, or both, which are treatments that assist the immune system. Evidence suggests a better immune response against melanoma when these combinations are used. Studies have shown that these combinations can help the body fight cancer by increasing the number of immune cells that attack tumors. In other trials with similar treatments, many patients experienced slower melanoma progression. While researchers continue to study VX15/2503, these early results are promising for those with advanced skin cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael Lowe, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with Stage IIIB-D melanoma that can be surgically removed. They must have certain blood cell counts, normal organ function tests, and agree to use contraception if of childbearing potential. Those who've had prior immunotherapy or certain other treatments are excluded, as well as those with severe medical conditions or a history of hypersensitivity to monoclonal antibodies.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My kidney function, measured by creatinine levels or clearance, is within the required range.

My cancer can be removed with surgery, and I am scheduled for a surgery evaluation.

Exclusion Criteria

I have or had immune-related lung, gut, liver, hormone glands, kidney, or skin conditions.

I have been cancer-free for over 5 years, or I had non-melanoma skin cancer/in situ carcinoma that was completely removed.

Prisoners and subjects who are compulsory detained.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VX15/2503 with or without ipilimumab and/or nivolumab, followed by surgery

7 weeks

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

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Follow-up at 90 days, every 12 weeks for 2 years, every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• VX15/2503

Trial Overview The study is testing the effectiveness of VX15/2503 alone or combined with ipilimumab and/or nivolumab in treating resectable melanoma. These drugs are types of monoclonal antibodies that may prevent tumor growth by targeting specific cells.

How Is the Trial Designed?

Group I: D (nivolumab, surgery) Experimental Treatment 2 Interventions

Participants receive nivolumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.

Group II: C (VX15/2503, nivolumab, ipilimumab, surgery) Experimental Treatment 4 Interventions

Participants receive VX15/2503 (pepinemab) IV over 60 minutes, nivolumab IV over 30 minutes, and ipilimumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.

Group III: B (VX15/2503, ipilimumab, surgery) Experimental Treatment 3 Interventions

Participants receive VX15/2503 (pepinemab) IV over 60 minutes and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.

Group IV: A (VX15/2503, nivolumab, surgery) Experimental Treatment 3 Interventions

Participants receive VX15/2503 (pepinemab) IV over 60 minutes and nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.

Group V: E (surgery) Active Control 1 Intervention

Participants undergo surgery.

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+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a study of 111 melanoma patients treated with immunotherapy or targeted therapy, the majority received immunotherapy, particularly anti-PD-1 treatments, with a total of 371 adverse events (AEs) reported.

The incidence of AEs was lower in patients receiving anti-PD-1 therapy, with only 15.3% experiencing severe (grade 3 to 4) AEs, which were more common in those on targeted therapies, highlighting the need for better reporting and understanding of both known and unknown AEs in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. Aguiar, JP., Cardoso Borges, F., Murteira, R., et al.[2021]

Two patients with BRAF V600E mutant melanoma treated with anti-PD-1 agents experienced no significant toxicity, highlighting the favorable safety profile of these immune checkpoint inhibitors as first-line therapy.

However, both patients developed severe hypersensitivity reactions and multi-organ injury after starting vemurafenib, indicating that clinicians should be cautious and monitor for potential toxicities when transitioning from anti-PD-1 therapy to BRAF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy. Johnson, DB., Wallender, EK., Cohen, DN., et al.[2021]

In a study of 93 Chinese patients with advanced melanoma treated with PD-1 inhibitors, those who developed immune-related adverse events (irAEs) had significantly higher overall response rates (ORR) and disease control rates (DCR) compared to those without irAEs.

Patients experiencing three or more irAEs showed even better clinical outcomes, including longer progression-free survival and overall survival, suggesting that the presence of irAEs may indicate a more effective immune response to PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. Zhao, JJ., Wen, XZ., Ding, Y., et al.[2021]

In a phase II trial involving 116 patients with metastatic Merkel cell carcinoma (mMCC), first-line treatment with avelumab resulted in a 39.7% objective response rate and a 30.2% durable response rate, indicating its efficacy in this aggressive skin cancer.

The treatment was generally well-tolerated, with 81% of patients experiencing treatment-related adverse events, but only 18.1% had severe (grade 3/4) events, and there were no treatment-related deaths, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. D'Angelo, SP., Lebbé, C., Mortier, L., et al.[2022]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

In a study analyzing over 91,000 adverse events from patients receiving immune checkpoint inhibitors, 10,933 cases of cutaneous immune-related adverse events (cirAEs) were identified, highlighting the prevalence and diversity of skin complications associated with immunotherapy.

The onset of cirAEs varies significantly by subtype, with some, like erythema multiforme and Stevens-Johnson syndrome, appearing around one month after treatment, while others, such as bullous pemphigoid and vitiligo, may take five to six months to develop.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study. Le, TK., Brown, I., Goldberg, R., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03769155?intr=pepinemab&rank=7

VX15/2503 With or Without Ipilimumab and/or Nivolumab ... This pilot phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab work in treating participants with stage IIIB-D ...

2. trials.braintumor.org trials.braintumor.org/trials/NCT03769155

VX15/2503 With or Without Ipilimumab and/or Nivolumab in ... This pilot phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab work in treating participants with stage IIIB-D ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.103

Neoadjuvant biomarker trial of pepinemab to enhance ... Neoadjuvant treatment with pepi enhanced the density and maturity of TLS deep within the tumor which was most prominent in combination with nivo notably in HPV ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03425461

Anti-SEMA4D Monoclonal Antibody VX15/2503 With ... This randomized pilot phase I trial studies the side effects and best dose of anti-SEMA4D monoclonal antibody VX15/2503 when given together with nivolumab ...

5. withpower.com withpower.com/trial/phase-1-skin-neoplasms-11-2018-e3a46

VX15/2503 + Immunotherapy for Skin Cancer · Info for Participants This pilot phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab work in treating participants with stage IIIB-D ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03425461

Anti-SEMA4D Monoclonal Antibody VX15/2503 With ... Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, nivolumab, and ipilimumab, may interfere with the ability of tumor cells to grow and ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT246939

Pilot integrated biomarker study of VX15/2503 in ... Pilot integrated biomarker study of VX15/2503 in combination with ipilimumab and/or nivolumab in patients with resectable metastatic melanoma. download.

8. clinicaltrial.be clinicaltrial.be/en/details/67001?only_active=0&only_eligible=0&only_recruiting=0&per_page=100

VX15/2503 in Combination With Ipilimumab or Nivolumab ... PRIMARY OBJECTIVE: To evaluate the effect of VX15/2503 alone and VX15/2503 in combination with immune checkpoint inhibitors, ipilimumab or ...