Opdualag vs Nivolumab for Skin Cancer

Overseen By Catherine O'Neil, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS metastases, Autoimmune disease, Cardiac disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like corticosteroids above a specific dose or other immunosuppressive medications within 30 days before starting the trial.

What data supports the effectiveness of the drug Nivolumab for skin cancer?

Nivolumab has shown to improve overall survival in patients with advanced melanoma, a type of skin cancer, and is effective as an adjuvant therapy for high-risk metastatic melanoma. It was the first drug of its kind to demonstrate long-term survival benefits in clinical trials for advanced melanoma patients. ^{1 2 3 4 5}

Is Opdualag (Nivolumab plus Relatlimab) safe for humans?

Nivolumab plus relatlimab has a manageable safety profile in patients with advanced melanoma, and nivolumab alone has been studied for safety in various conditions, showing some immune-related side effects like skin issues. ^{6 7 8 9 10}

How does the drug Opdualag differ from other treatments for skin cancer?

Opdualag is unique because it combines two drugs, nivolumab and relatlimab, which target different immune checkpoints to enhance the body's immune response against cancer. Nivolumab targets the PD-1 receptor, while relatlimab targets the LAG-3 protein, making this combination a novel approach compared to treatments that target only one checkpoint. ^{11 12 13 14 15}

What is the purpose of this trial?

This is a Phase 2 clinical trial with a 2:1 randomization comparing neoadjuvant Nivolumab + Relatlimab (Opdualag) vs neoadjuvant Nivolumab in patients with resectable high risk BCC (HR BCC)

Research Team

Soo Park, MD

Principal Investigator

UC San Diego Health - Moores Cancer Center

Eligibility Criteria

This trial is for adults over 18 with a specific skin cancer called high-risk basal cell carcinoma (HR BCC) that's big enough to need surgery and might cause cosmetic or functional issues. Participants must be treatment-naive, able to understand the study, and sign consent. They should also have good physical function and adequate blood cell counts.

Inclusion Criteria

I can understand and am willing to sign the consent form.

My cancer is confirmed as basal cell carcinoma through testing.

My platelet count is at least 100,000 per microliter.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive 4 cycles of neoadjuvant Opdualag or Nivolumab every 4 weeks, with an option to proceed to surgery after 2 cycles if there is disease progression.

16 weeks

Surgical Resection

Surgical resection is performed after treatment cycles, unless a clinical complete response is observed.

Follow-up

Participants are monitored for disease recurrence and other secondary outcomes.

2 years

Extension

Option to continue with Opdualag or Nivolumab beyond 4 cycles if there is ongoing clinical benefit.

Treatment Details

Interventions

• Nivolumab
• Relatlimab

Trial Overview The trial is testing two treatments before surgery: Opdualag (a combination of Nivolumab + Relatlimab) versus just Nivolumab alone in patients with HR BCC. Patients are randomly assigned to one of these treatments at a ratio of 2:1.

Participant Groups

Group I: Cohort 2 Experimental Treatment 1 Intervention

Nivolumab 480 mg IV. Every 4 weeks, up to 4 cycles

Group II: Cohort 1 Experimental Treatment 1 Intervention

Nivolumab 480 mg IV and Relatlimab 160 mg IV. Every 4 weeks, up to 4 cycles

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Findings from Research

Nivolumab treatment resulted in an increased overall survival rate of 7.5 months compared to 5.1 months for the control group, indicating its efficacy in extending life for patients.

Patients receiving nivolumab also reported a better quality of life, suggesting that the treatment not only prolongs survival but also improves the well-being of those undergoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

In a real-world study of 709 patients with advanced melanoma treated with ipilimumab plus nivolumab, 50.7% experienced severe treatment-related adverse events, highlighting the need for careful monitoring during therapy.

Despite the high rate of adverse events, the combination therapy showed promising long-term survival outcomes, with a median overall survival of 28.7 months and a 4-year overall survival rate of 50% for patients similar to those in the CheckMate-067 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands. van Zeijl, MCT., van Breeschoten, J., de Wreede, LC., et al.[2023]

In a study of 37 patients with stage IV metastatic melanoma, high levels of soluble CD73 (sCD73) enzyme activity in the serum were linked to significantly poorer overall survival and progression-free survival when treated with nivolumab.

Patients with high sCD73 activity had a median progression-free survival of only 2.6 months compared to 14.2 months for those with lower activity, suggesting that measuring sCD73 could help predict how well patients will respond to nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. Morello, S., Capone, M., Sorrentino, C., et al.[2018]

In a study of 40 patients with metastatic melanoma who progressed after anti-PD-1 therapy, 10% achieved an objective response to subsequent treatment with ipilimumab, and 8% experienced prolonged stable disease for over 6 months.

However, 35% of patients developed severe immune-related toxicities, with the most common being diarrhea, and 7% experienced life-threatening pneumonitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. Bowyer, S., Prithviraj, P., Lorigan, P., et al.[2021]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

In a study of 108 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab, those who experienced immune-related adverse events (irAEs) had a significantly higher objective response rate (ORR) of 46.3% compared to 19.4% in those without irAEs.

Patients with irAEs also showed longer median progression-free and overall survival rates, suggesting that the occurrence of irAEs may be a useful indicator of the treatment's effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. Matsuo, M., Yasumatsu, R., Masuda, M., et al.[2020]

Over 40% of melanoma patients treated with anti-PD-1 therapy experience dermatologic immune-related adverse events (irAEs), but these are typically self-limiting and manageable, with common issues including rashes and itching.

Both anti-PD-1 and anti-PD-L1 antibodies show a similar dermatologic safety profile, and while these skin reactions are frequent, they rarely lead to severe complications or the need to stop treatment, highlighting the importance of early recognition and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Sibaud, V., Meyer, N., Lamant, L., et al.[2022]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab plus relatlimab is a combination immunotherapy that targets immune checkpoints, specifically PD-1 and LAG-3, and has been approved for treating unresectable or metastatic melanoma in adults and adolescents weighing at least 40 kg.

This combination therapy represents a significant advancement in cancer treatment, as it utilizes two different mechanisms to enhance the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. Paik, J.[2022]

References

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

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

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

Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands. [2023]

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

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

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

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. [2022]

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

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

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

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. [2020]

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

Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. [2022]

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

Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. [2022]

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Comparative Efficacy and Safety of PD-1/PD-L1 Inhibitors for Patients with Solid Tumors: A Systematic Review and Bayesian Network Meta-analysis. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients. [2021]