Neoadjuvant Cemiplimab Plus Imiquimod in Cutaneous Basal Cell Carcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instituto Oncologico Dr. Rosell S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Neoplasms [C04]

Trial duration

22 Oct 2025 → ongoing

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective for the Phase Ib part of the trial is to evaluate the safety and toxicity of the combination of intravenous cemiplimab plus topical imiquimod (plus fractional laser therapy) as neoadjuvant treatment in patients with high risk and potentially resectable BCC.
The primary objective for the Phase II of the trial it to evaluate the antitumoral activity in terms of 3-years rate of relapse-free survival (RFS) according to RECIST 1.1 (Appendix 3) of intravenous cemiplimab as single therapy or in combination with topical imiquimod (plus fractional laser therapy) as neoadjuvant treatment in patients with high risk and potentially resectable BCC.

Secondary objectives 7

1. Phase Ib: ● To evaluate pathological complete response rate (pCR) according to Immune-Related Pathologic Response Criteria' (irPRC) criteria (Appendix 4) as surrogate of efficacy at short follow-up.
2. To evaluate the activity in terms of response rate (RECIST 1.1), duration of response, clinical benefit, RFS/PFS and OS.
3. To evaluate the rate of resectability (downstaging) of BCC after 4 cycles of treatment.
4. Phase II: To evaluate pathological complete response rate (pCR) according to Immune-Related Pathologic Response Criteria' (irPRC) criteria (Appendix 4) as surrogate of efficacy at short follow-up.
5. To evaluate the activity in terms of response rate (RECIST 1.1), duration of response, clinical benefit, and OS.
6. To evaluate safety of the intended treatment regimen based on the frequency and severity of adverse events and Treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0 (Appendix 5).
7. To evaluate the rate of resectability (downstaging) of BCC after 4 cycles of treatment.

Conditions and MedDRA coding

Cutaneous Basal Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Male/female participants who are at least 18 years of age on the day of signing informed consent.
2. 2. Histologically confirmed diagnosis of basal cell carcinoma (BCC), potentially resectable with curative intention. a. The definition of resectability will be determined locally by the surgeon according to his/her criteria and local standard guidelines. The validated classification from University Hospital of Lille should be used for guidance in resectability assessment (Appendix 11). b. Surgery would be recommended in routine clinical practice.
3. 3. Patient should be considered as high risk, defined as: a. at least 1 large (≥ 2 cm in diameter in trunk/extremities or any size in Head, neck, hands, feet, pretibial, and anogenital) still resectable, but with increased risk for cosmetic disfigurement or functional defects by assessment of the enrolling physician. b. Having basosquamous, infiltrative, sclerosing/morpheaform, micronodular, and BCC with carcinosarcomatous differentiation features in any portion of the tumor. c. Patients with large (≥ 3 cm in diameter in areas of intermedium risk of recurrence such as forehead, cheek, chin, neck, scalp or ≥ 5 cm for lesions in trunk/extremities) recurrent basal cell carcinoma are also eligible. d. Multicentric tumors that would require a cosmetic disfigurement or functional defects by assessment of the enrolling physician will be eligible.
4. 4. At least one measurable lesion by RECIST v1.1 (Appendix 3).
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
6. 6. Life expectancy of at least 24 weeks.
7. 7. Pretreatment tumor tissue sample available. Note: If the biopsy is considered by the investigator to pose an unacceptable safety risk to the patient or would compromise tumor measurements, the biopsy requirement may be waived for an individual patient after notification of the medical monitor. For patients without on-study screening biopsy, an archival FFPE tissue sample (block or 25 unstained slides) should be provided.
8. 8. Adequate normal organ and marrow function as defined below: a. Absolute neutrophil count ≥ 1.5 x 10 9 cells/L b. Platelets ≥ 75 x 10 e. Thyroid stimulating hormone (TSH) within normal limits, or Total triiodothyronine (T3) is within normal limits, or Free T3 and free thyroxine (T4) are within the normal limits f. Total bilirubin ≤ 2 x ULN (except patients with documented Gilbert's syndrome; up to 3 x ULN) g. Creatinine < 2 mg/dl (or a glomerular filtration rate > 60) 9 /L c. Hemoglobin ≥ 8 g/dL d. Aspartate and alanine aminotransferases (AST, ALT) ≤ 3 x upper limit of normal (ULN) and alkaline phosphatase <2.5x ULN
9. 9. Female patients of childbearing potential (WOCBP) must provide a negative urine pregnancy test 72 hours prior to the first administration of study treatment, and must agree to: (I) use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%; refer to Appendix 6); (II) refrain from donating ovules; and (III) refrain from breastfeeding for the duration of the study treatment and for 180 days after the last dose of cemiplimab.
10. 10. Male participants of reproductive potential are eligible to participate if they agree to the following starting with the first dose of study treatment through at least 180 days (a spermatogenesis cycle) after the last dose of study treatment: a. Refrain from donating sperm plus, either: b. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent, or c. Must agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak, when having sexual intercourse with a WOCBP who is not currently pregnant.

Exclusion criteria 16

1. 1. Distant metastatic disease (M1), visceral and/or distant nodal.
2. 2. Patients who have another malignancy that is progressing or requires active treatment, except: a. Non-melanoma skin cancer that has undergone potentially curative therapy b. In situ cervical carcinoma c. Any tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy).
3. 3. Patients who have received a previous systemic treatment for cancer within the last previous 3 months or 5 half-lives (whichever is latest), including immunotherapy, prior to initiation of dosing within this protocol.
4. 4. History of, or significant evidence of risk for, severe chronic inflammatory or autoimmune disease. Note: Patients with vitiligo, type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, childhood asthma that has resolved, or psoriasis that does not require systemic treatment are permitted.
5. 5. Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization. Note: Patients should remain on antiviral therapy throughout trial treatment and follow.
6. 6. Patients with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
7. 7. Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 100 on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
8. 8. Active tuberculosis.
9. 9. Receipt of a live vaccine within 28 days of enrollment.
10. 10. Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
11. 11. Recipient of a solid organ transplant (other than corneal transplants).
12. 12. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
13. 13. Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment. Notes: Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent. Inhaled or topical steroids at standard doses are allowed. Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study.
14. 14. Has participated in a study of an investigational agent or an investigational device within 4 weeks of enrollment.
15. 15. Dementia or significantly altered mental status, or any social or economic conditions that would prohibit or interfere with the understanding or rendering of informed consent and compliance with the requirements of this protocol.
16. 16. Female patients who are pregnant or breast-feeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase Ib: ● The primary endpoint is the incidence of adverse events (AE) and treatment-related AEs (TRAEs) assessed by NCI CTCAE v5.0 (Appendix 5).
2. Phase II: ● The primary endpoint RFS rate at 3 years, defined as the proportion of patients free of locoregional progression or recurrence, distant metastasis (RECIST v 1.1; Appendix 3) or death due to any cause at 3-years from the date of study treatment initiation.

Secondary endpoints 14

1. Phase Ib: ● Pathological response assessment: proportion of patients with pathologic complete response (pCR) per Immune-Related Pathologic Response Criteria' (irPRC) criteria (Appendix 4): 0% residual viable tumor (RVT) remaining in post-therapy specimen (no signs of cancer) in tissue samples removed during surgery.
2. Objective response rate (ORR)
3. Clinical benefit rate (CBR)
4. Duration of clinical benefit (DBC)
5. Relapse-free survival (RFS)
6. Overall survival (OS)
7. Phase II: ● Pathologic complete response (pCR)
8. Objective response rate (ORR)
9. Clinical benefit rate (CBR)
10. Duration of clinical benefit (DBC)
11. Rate of resectability, downstaging
12. Overall survival (OS)
13. Adverse events (AE)
14. Treatment-related AEs (TRAEs)

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto Oncologico Dr. Rosell S.L.

Sponsor organisation

Instituto Oncologico Dr. Rosell S.L.

Address

Calle De Sabino Arana Num. 5

City

Barcelona

Postcode

08028

Country

Spain

Scientific contact point

Organisation

Instituto Oncologico Dr. Rosell S.L.

Contact name

MFAR Clinical Reseach S.L.

Public contact point

Organisation

Instituto Oncologico Dr. Rosell S.L.

Contact name

Federico Nepote

Locations

1 EU/EEA country · 4 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 8 files

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

Application history

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