Cemiplimab for Cutaneous T-Cell Lymphoma

(BIOSELECT Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AHS Cancer Control Alberta

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Hepatitis, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 51 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

Background - Advanced cutaneous T-cell lymphoma (mycosis fungoides, MF) is an incurable extranodal mature lymphoma with poor prognosis. Currently available therapies provide only short-term remissions. Rationale - MF is an immunogenic cancer and expresses a high number of neoantigens. therefore it it reasonable to assume that it would respond to immune checkpoint inhibitors. Objectives - The primary objective is to test the clinical efficacy (objective response rate) of the immune checkpoint inhibitor cemiplimab in patients with advanced mycosis fungoides (MF) who failed first-line therapy, defined as the sum of complete and partial responses (where at least 50% reduction of mSWAT is achieved).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on immunosuppressive agents or systemic corticosteroids, you may need to stop them at least 30 days before starting the trial.

What data supports the effectiveness of the drug cemiplimab for treating cutaneous T-cell lymphoma?

While there is no direct data on cemiplimab for cutaneous T-cell lymphoma, similar treatments like monoclonal antibodies have shown promise in treating advanced stages of this condition. For example, drugs like mogamulizumab and brentuximab vedotin, which are also monoclonal antibodies, have been approved for use in certain types of cutaneous T-cell lymphoma, suggesting that cemiplimab might also be effective. ^{1 2 3 4 5}

Is cemiplimab generally safe for humans?

Cemiplimab has been shown to have an acceptable safety profile in clinical trials for advanced cutaneous squamous cell carcinoma, with most side effects being manageable. The rate of treatment discontinuation due to side effects was low, and the drug was associated with low rates of serious adverse events. ^{6 7 8 9 10}

How is the drug cemiplimab different from other treatments for cutaneous T-cell lymphoma?

Cemiplimab is unique because it is a checkpoint inhibitor, which helps the immune system recognize and attack cancer cells, offering a novel approach compared to traditional therapies that often have low response rates and short durations of effectiveness. ^{11 12 13 14 15}

Eligibility Criteria

Adults with advanced cutaneous T-cell lymphoma (mycosis fungoides) who have not responded to at least one prior therapy can join this trial. They must be able to consent, follow the study plan, and use effective birth control if of childbearing potential. People with certain organ dysfunctions or those taking immunosuppressants cannot participate.

Inclusion Criteria

I have tried at least one treatment before that didn't work.

My skin cancer (mycosis fungoides) is confirmed by a specialized board.

My organ functions are within normal ranges.

Exclusion Criteria

I have recently used drugs that weaken my immune system.

I need radiation therapy along with other treatments.

I have a serious heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cemiplimab 350 mg intravenously every 21 days

Up to 51 weeks

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

99 weeks

Regular visits as per study protocol

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Cemiplimab

Trial Overview The trial is testing cemiplimab's effectiveness in treating mycosis fungoides after other treatments have failed. It aims to see how well patients respond by measuring the reduction in their skin tumors.

Participant Groups

Group I: Cemiplimab Experimental Treatment 1 Intervention

Study treatment includes administration of cemiplimab 350 mg intravenous every 21 days (+/﹣ 3 days)

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?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Findings from Research

In a study of 118 patients with cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS), the overall survival for MF patients was 17.7 years, while SS patients had a median survival of 3.5 years, indicating significant differences in outcomes based on the type of CTCL.

The most common treatments for MF included low-dose methotrexate and interferon-alpha, while SS patients often received bexarotene and extracorporeal photopheresis, highlighting the need for more innovative therapies to be integrated into earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience. Polgárová, K., Polívka, J., Kodet, O., et al.[2022]

Cutaneous T-cell lymphomas (CTCL), particularly Mycosis fungoides (MF) and cutaneous CD30+ lymphoproliferative disorders, account for 80% of CTCL cases, and their treatment varies significantly based on disease stage, with early-stage therapies focusing on skin-directed treatments and advanced stages requiring systemic therapies.

Novel targeted therapies, such as mogamulizumab and brentuximab vedotin, are important for treating CTCL and highlight the role of biomarkers like CD30 in both diagnosis and therapy, improving treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous T-cell lymphomas-An update 2021. Kempf, W., Mitteldorf, C.[2021]

Recent advancements in the understanding of cutaneous T-cell lymphomas (CTCL) have led to the identification of new therapeutic targets, including monoclonal antibody therapies like brentuximab vedotin and mogamulizumab, which have received FDA approvals for specific CTCL subtypes.

Current treatments for early-stage CTCL primarily involve skin-directed therapies, but there is a lack of long-term curative options for advanced disease, highlighting the importance of ongoing research into new therapies such as immune checkpoint inhibitors and additional monoclonal antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Existing and Emerging Therapies for Cutaneous T-Cell Lymphoma. Van-de-Velde, V., Zhou, Y.[2019]

The collaboration between dermatologists and oncologists has led to the establishment of supportive oncodermatology clinics, which focus on managing skin toxicities associated with targeted therapies for blood cancers.

A systematic review of various targeted therapies revealed distinct cutaneous adverse event profiles, emphasizing the need for early diagnosis and management to enhance treatment tolerability and patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies. Ransohoff, JD., Kwong, BY.[2018]

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 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 (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]

In a study of 11 patients with cutaneous T-cell lymphoma (CTCL), 90.9% showed significant improvement in their skin lesions after treatment with oral alitretinoin, with an average response time of 2.5 months.

Alitretinoin was generally well tolerated, with only a few patients experiencing mild side effects, suggesting it could be a promising treatment option for CTCL with a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cutaneous T-cell lymphoma with oral alitretinoin. Kapser, C., Herzinger, T., Ruzicka, T., et al.[2018]

References

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

Novel therapeutic strategies for cutaneous T-cell lymphoma in advanced stages. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience. [2022]

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

Phase II trial of proteasome inhibitor bortezomib in patients with relapsed or refractory cutaneous T-cell lymphoma. [2015]

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

Cutaneous T-cell lymphomas-An update 2021. [2021]

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

Existing and Emerging Therapies for Cutaneous T-Cell Lymphoma. [2019]

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

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies. [2018]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Cemiplimab: First Global Approval. [2023]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Cutaneous T cell lymphoma: update on treatment. [2012]

12. England pubmed.ncbi.nlm.nih.gov

Treatment of cutaneous T-cell lymphoma with oral alitretinoin. [2018]

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

Novel therapies targeting cutaneous T cell lymphomas and their microenvironment. [2022]

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

Treatment of cutaneous T-cell lymphoma: an update. [2015]

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

Therapeutic advances in biological response modifiers in the treatment of cutaneous T-cell lymphoma. [2018]