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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Jul 2025 → ongoing

Decision date (initial)

2025-02-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The assessment of the efficacy of Cemiplimab when applied as first-line treatment in advanced, HHI naïve BCC measured by objective response rate (ORR) after 6 months of treatment.

Secondary objectives 3

1. The further assessment of the efficacy of Cemiplimab as first-line treatment in advanced BCC by ORR, progression-free survival (PFS), duration of response (DoR), overall survival (OS) and time to next systemic treatment (TTNsT).
2. To evaluate the safety and tolerability of Cemiplimab as first-line treatment in advanced BCC.
3. Determination of molecular biomarkers and their correlation with ORR by assessing e.g., gene expression signatures, tumor mutational burden including mutational signatures as well as morphological and cellular characteristics of the tumor microenvironment.

Conditions and MedDRA coding

basal cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Signed informed consent form available.
2. 2. Patient* 18 years or older at time of signing informed consent form. * There are no data that indicate special gender distribution. *Therefore, patients will be enrolled in the study gender-independently
3. 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. 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. 5. Expected survival of at least 6 months
6. 6. ECOG performance status 0 or 1
7. 7. Adequate laboratory parameters particularly for the blood count, renal and liver function parameters. a) Absolute number of neutrophils ≥ 1.5 x 109/L b) Platelets ≥ 75 x 109/L c) Hemoglobin ≥ 9 g/dL d) 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) e) AST (SGOT) and ALT (SGPT) ≤ 3x ULN f) AP ≤ 2.5x ULN g) Serum creatinine ≤ 2x ULN or creatinine clearance ≥ 40 mL/min
8. 8. Absence of other severe comorbidities
9. 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. 10. Negative serum pregnancy test done less than or equal to 7 days prior to enrollment, for females of childbearing potential only.
11. 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

Exclusion criteria 16

1. 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. 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. 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. 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. 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. 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. 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 remin 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. 8. History of pneumonitis within the last 3 years
9. 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. 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. 11. Receipt of live vaccines (including attenuated) within 30 days of first administration of Cemiplimab
12. 12. Pregnancy or lactation period.
13. 13. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
14. 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. 15. Legal incapacity or limited legal capacity.
16. 16. On-treatment participation in another clinical trial in the period 30 days prior to start of the study treatment and during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR@6months is defined as the rate of patients assessed with complete or partial response (CR or PR) according to ERIVANCE-like criteria as best overall response, relative to the total number of patients as evaluated 6 months after treatment allocation.

Secondary endpoints 12

1. ORR is defined as the rate of patients assessed with complete or partial response (CR or PR) as best overall response, relative to the total number of patients.
2. PFS is defined as time from date of allocation to treatment to the date of the first objectively documented tumor progression, as determined by investigators, or death due to any cause.
3. DoR is defined as length of time from initial response (CR/PR) to first objectively documented progression or death.
4. OS defined as time from date of allocation to treatment until the date of death from any cause.
5. Time to next systemic treatment is defined as time from date of allocation to treatment to initiation of the next line of systemic therapy.
6. Incidence of adverse events and serious adverse events
7. Severity of adverse events by CTCAE v5.0 grade
8. Relationship of adverse events to Cemiplimab
9. Incidence of adverse events and serious adverse events
10. Severity of adverse events by CTCAE v5.0 grade
11. Relationship of adverse events to Cemiplimab
12. Tissue samples may be used for the following analyses: - Morphology (H&E and trichrome/connective tissue stain) - Multiplexed immunofluoresence with panels addressing T-cell activation and differentiation as well as the immunomodulating tumor microenvironment - Transcriptomics (EdgeSeq-based mRNA expression) - Infered tumor mutational burden (TMB) - TCR repertoire. Blood samples will be used for TCR repertoire analysis at the central biomarker laboratory.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Sponsor organisation

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Address

Steinbacher Hohl 2-26, Praunheim Praunheim

City

Frankfurt Am Main

Postcode

60488

Country

Germany

Scientific contact point

Organisation

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical Trial project manager

Public contact point

Organisation

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical Trial project manager

Third parties 2

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications