Cemiplimab + RP1 for Advanced Squamous Skin Cancer

(CERPASS Trial)

Recruiting at 78 trial locations

Overseen By Clinical Trials at Replimune

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Replimune Inc.

Must not be taking: Anti-herpetics, Immunosuppressives

Disqualifiers: Autoimmune disease, Hepatitis, HIV, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

231 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, but you cannot participate if you need to use certain antiviral medications or have had specific treatments like PD-1/PD-L1 blockers. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Cemiplimab for advanced squamous skin cancer?

Cemiplimab has been shown to be effective in treating advanced cutaneous squamous cell carcinoma, with studies indicating it improves survival and has substantial antitumor activity. It is approved by the FDA for patients who cannot undergo surgery or radiation, and it has demonstrated benefits over other treatments like EGFR inhibitors and chemotherapy. ^{1 2 3 4 5}

Is the combination of Cemiplimab and RP1 safe for treating advanced squamous skin cancer?

Cemiplimab, also known as Libtayo, has been shown to be generally safe in humans, with most side effects being manageable. Common side effects include fatigue, diarrhea, itching, and rash, while severe side effects are rare and include inflammation of the lungs, heart, muscles, and liver. The risk of treatment-related death is low, at about 3% in clinical trials. ^{1 2 6 7 8}

What makes the drug cemiplimab unique for treating advanced squamous skin cancer?

Cemiplimab is unique because it is the first approved drug specifically for advanced cutaneous squamous cell carcinoma, working by blocking a protein called PD-1 to help the immune system attack cancer cells. It is administered intravenously and has shown significant and durable responses in patients who cannot undergo surgery or radiation. ^{1 2 6 7 9}

What is the purpose of this trial?

To estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or metastatic CSCC, as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.

Research Team

Moran Mishal, MD

Principal Investigator

Lead Medical Monitor

Jeannie Hou, MD

Principal Investigator

Secondary Medical Monitor

Eligibility Criteria

This trial is for adults with advanced squamous skin cancer who can't have or don't want surgery/radiotherapy. They should be relatively active (ECOG ≤1), expected to live more than 12 weeks, and able to provide a tumor sample. Not allowed if they've had certain previous treatments, active brain metastases, lung inflammation in the last 5 years, recent vaccines, herpes complications, need anti-herpetic drugs regularly, significant autoimmune disease treated with immunosuppressants within 5 years, or have hepatitis B/C or HIV.

Inclusion Criteria

Anticipated life expectancy >12 weeks

I have at least one tumor that can be measured and treated according to the study.

I agree to provide samples of my tumor for review.

Exclusion Criteria

I haven't had immune therapy for my condition in the last 3 years, except as part of initial treatment.

I do not have active hepatitis B, hepatitis C, or HIV.

I have had serious herpes infections or complications like eye or brain infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab monotherapy or cemiplimab in combination with RP1, administered every 3 weeks

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cemiplimab
• RP1

Trial Overview The study compares two approaches: Cemiplimab alone versus combined with RP1 in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). The main focus is on how well these treatments shrink tumors according to independent reviews.

Participant Groups

Group I: Cemiplimab in combination with RP1 Experimental Treatment 2 Interventions

Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks

Group II: Cemiplimab Active Control 1 Intervention

Cemiplimab administered intravenously as a single therapy every 3 weeks

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

Cemiplimab demonstrated a significant objective response rate of 46.1% in patients with advanced cutaneous squamous cell carcinoma (CSCC), with complete response rates of 20.3% for metastatic CSCC and 12.8% for locally advanced CSCC, indicating its efficacy as a treatment option.

Patients experienced durable improvements in quality of life and pain control, with significant enhancements observed as early as the second treatment cycle, highlighting the treatment's positive impact on overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. Rischin, D., Khushalani, NI., Schmults, CD., et al.[2022]

Cemiplimab, a PD-1 inhibitor, shows significant improvements in overall survival (OS) and progression-free survival (PFS) compared to EGFR inhibitors and pembrolizumab, with hazard ratios indicating a strong benefit.

In comparison to platinum-based chemotherapy, cemiplimab also demonstrated superior efficacy in improving overall survival for patients with advanced cutaneous squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. Keeping, S., Xu, Y., Chen, CI., et al.[2021]

Cemiplimab demonstrated significant antitumor activity in patients with locally advanced cutaneous squamous cell carcinoma, with 44% of the 78 patients showing an objective response, including 13% achieving a complete response.

The treatment had an acceptable safety profile, with 44% of patients experiencing grade 3-4 adverse events, the most common being hypertension and pneumonia, and one treatment-related death due to aspiration pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Migden, MR., Khushalani, NI., Chang, ALS., et al.[2021]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

Cemiplimab, an antibody treatment for locally advanced and metastatic cutaneous squamous cell carcinoma, shows promising efficacy with objective response rates between 32% and 77%, indicating it is a viable option for patients who cannot undergo surgery or radiation.

The treatment is generally safe and well-tolerated, with only 9.8% of patients experiencing adverse events severe enough to stop therapy, although there is a 3% risk of treatment-related death due to immune-mediated side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives. Mager, L., Gardeen, S., Carr, DR., et al.[2023]

Cemiplimab, a PD-1 targeting monoclonal antibody, demonstrated an objective response rate of 45.5% in a real-life study of 33 patients with advanced cutaneous squamous cell carcinoma, confirming its efficacy as a treatment option.

The addition of radiotherapy to cemiplimab resulted in a quicker response time, with a median duration of response of 5.5 months compared to 3 months for cemiplimab alone, and did not increase adverse events, indicating a safe and effective combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study. Bailly-Caillé, B., Kottler, D., Morello, R., et al.[2023]

References

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

Cemiplimab: First Global Approval. [2023]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

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

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. [2022]

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

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. [2021]

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

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

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

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. [2020]

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

Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study. [2023]