Cemiplimab as first-line treatment for advanced basal cell carcinoma

Evaluation of Efficacy and Safety of Cemiplimab as First Line Treatment for Advanced Basal Cell Carcinoma (CEMI-first) - An Open Label, Single Arm, Prospective Phase II Trial of the DeCOG Network

This trial will try cemiplimab as a first-line treatment for adults with locally advanced basal cell carcinoma who have not received hedgehog inhibitors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest (Academic / other)
• Drugs / interventions: Cemiplimab, immunotherapy, radiation, prednisone
• Locations: 7 sites (Erfurt and 6 other locations)
• Trial ID: NCT06981325 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm, multicenter phase II trial gives cemiplimab 350 mg IV on day 1 of each 21-day cycle for up to 12 months (maximum 17 cycles) to adults with centrally confirmed, locally advanced BCC who are hedgehog-inhibitor–naïve. Tumor response will be assessed every 12 weeks and the primary endpoint is objective response rate after six months, with safety and tolerability as secondary endpoints. Tumor tissue will be collected for translational research to identify potential biomarkers correlated with response. Patients will be followed until death or for up to 12 months after the last dose.

Who should consider this trial

Good fit: Adults (≥18 years) with centrally confirmed locally advanced BCC not amenable to or refusing surgery/radiotherapy, who are HHI‑naïve, have ECOG 0–1, adequate laboratory function, and an expected survival of at least 6 months.

Not a fit: Patients with distant metastases, prior hedgehog-inhibitor therapy, poor performance status (ECOG ≥2), or significant organ dysfunction are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, this could enable tumor shrinkage or durable disease control with an immune checkpoint inhibitor used up front, offering a non-surgical treatment option for advanced BCC.

How similar studies have performed: Other anti–PD‑1 therapies have shown activity in advanced BCC and cemiplimab has shown promising results in HHI‑pretreated patients, so first-line use is relatively novel but grounded in prior activity of this class.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent form available
2. Patient\* 18 years or older at time of signing informed consent form
3. Centrally confirmed histological diagnosis of BCC

   NOTE: Tumor tissue to be sent to Central Pathology during screening procedure:
   * Formalin-fixed, parrafin-embedded (FFPE) tumor specimen in a paraffin block (preferred) OR
   * approximately 10 sections (5µm thickness) on uncoated slides and 10 sections (5µm thickness) on Superfrost Ultra slides containing unstained, freshly cut, serial sections to be submitted along with associated pathology report (please refer to section 11.1.1 for details)
4. Locally advanced stage without distant metastases, not amenable for surgery or radiotherapy or surgery/radiotherapy contraindicated or refused by patient (as evidenced in source data)
5. Expected survival of at least 6 months
6. ECOG performance status 0 or 1
7. Adequate laboratory parameters particularly for the blood count, renal and liver function parameters.

   1. Absolute number of neutrophils ≥ 1.5 x 109/L
   2. Platelets ≥ 75 x 109/L
   3. Hemoglobin ≥ 9 g/dL
   4. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), (patients with Gilbert´s Disease and total bilirubin up to 3x ULN may be eligible after approval from trial's medical expert)
   5. AST (SGOT) and ALT (SGPT) ≤ 3x ULN
   6. AP ≤ 2.5x ULN
   7. Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL/min
8. Absence of other severe comorbidities
9. Resolution of any acute, clinically significant treatment-related adverse events from prior therapy/procedure to Grade ≤ 1 prior to study entry, with the exception of alopecia.
10. Negative serum pregnancy test done less than or equal to 7 days prior to enrollment, for females of childbearing potential only.
11. Sexually active women of childbearing potential (WOCBP) and men with WOCBP partners must be prepared to use suitable contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 6 months after the last dose of Cemiplimab

    * There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently

Exclusion Criteria:

1. Pretreatment with systemic immunotherapy (such as PD-1/PD-L1 or CTL4) or targeted therapy (such as hedgehog inhibitor) NOTE: Prior treatment with imiquimod or other topical or intralesional immune modulators will not be exclusionary
2. Any other non-radiation anti-cancer therapy (e.g. imiquimod, photodynamic therapy; neither investigational nor standard of care) within 30 days (from date of last administration) of initial Cemiplimab administration or if planned during the study duration
3. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required systemic immunosuppressive therapy, excluding: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism requiring only hormone replacement, or psoriasis that does not require systemic treatment
4. Other neoplasia, in particular hematologic diseases that might impair immune response, such as chronic lymphocytic leukemia, myelodysplastic or myeloproliferative disease and patients with Gorlin-Goltz syndrom
5. Immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of Cemiplimab NOTE: Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are eligible for participation. Furthermore, patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or replacement in case of adrenal or hypophysis insufficiency are eligible for participation.
6. Known allergic/hypersensitive reaction to the study drug and any of its excipients or history of documented allergic/hypersensitive reactions to antibody treatments
7. Active infection requiring systemic therapy, including uncontrolled HIV, HBV and HCV infection or diagnosis of immunodeficiency.

   NOTE: Patients are eligible if:
   * Patients have controlled HIV infection with CD4 counts is \> 350 cells/µL and viral load is undectable \[HIV RNA PCR\]
   * Patients positive for HBV surface antigen have controlled HBV infection receiving anti-viral therapy and with undectable serum viral load \[HBV DNA PCR\]. Patients must remain on anti-viral therapy for at least 6 months after last dose of Cemiplimab
   * Patients positive for HCV antibody have controlled HCV infection with undectable viral load \[HCV RNA PCR\]
8. History of pneumonitis within the last 3 years
9. Patients with history of solid organ transplant (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the Lead Investigator)
10. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
11. Receipt of live vaccines (including attenuated) within 30 days of first administration of Cemiplimab
12. Pregnancy or lactation period.
13. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
14. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
15. Legal incapacity or limited legal capacity.
16. On-treatment participation in another clinical trial in the period 30 days prior to start of the study treatment and during the study

Where this trial is running

Erfurt and 6 other locations

• Helios Klinikum Erfurt — Erfurt, Germany (Recruiting)
• Universitätsklinikum Erlangen — Erlangen, Germany (Recruiting)
• Nationales Centrum für Tumorerkrankungen (NCT) — Heidelberg, Germany (Recruiting)
• Universitätsklinikum Leipzig — Leipzig, Germany (Recruiting)
• Johannes Wesling Klinikum — Minden, Germany (Recruiting)
• Helios Klinikum Oberhausen — Oberhausen, Germany (Recruiting)
• Universitätsklinikum Tübingen — Tübingen, Germany (Recruiting)

Study contacts

• Principal investigator: Ralf Gutzmer, Prof. Dr. med. — Johannes Wesling Klinikum Minden
• Study coordinator: Ralf Gutzmer, Prof. Dr. med.

Conditions Basal Cell Carcinoma; First Line Treatment; BCC; Skin Cancer; anti-PD-1 monoclonal antibody; HHI naïve; Cemiplimab