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

41 Participants Needed

Trial Summary

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.

What safety data exists for VX15/2503 + Immunotherapy for Skin Cancer?

Immunotherapy drugs like Ipilimumab (Yervoy) and Nivolumab (Opdivo) can cause skin-related side effects, such as rashes and vitiligo (loss of skin color), which are common but usually mild. Severe skin reactions are rare but can occur. These treatments have been used in various cancers, and while they are generally considered safe, they can lead to immune-related side effects that vary in severity. ^{1 2 3 4 5}

How is the drug VX15/2503 (Pepinemab) different from other skin cancer treatments?

The treatment VX15/2503 (Pepinemab) is unique because it combines with immunotherapy to potentially enhance the body's immune response against skin cancer, which may offer a novel approach compared to existing treatments that primarily focus on targeting cancer cells directly. ^{6 7 8 9 10}

What is the purpose of this trial?

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 melanoma that can be removed by surgery. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab may interfere with the ability of tumor cells to grow and spread.

Research Team

Michael Lowe, MD

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

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

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study. [2023]

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

Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Vitiligoid hypopigmentation associated with pembrolizumab in metastatic head and neck cancer. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. [2021]

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

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. [2021]

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

Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program. [2023]

7. England 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. [2022]

8. United States 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Avelumab treatment in Italian patients with metastatic Merkel cell carcinoma: experience from an expanded access program. [2021]