Cemiplimab Plus Imiquimod and Laser Therapy As Neoadjuvant Treatment In Cutaneous Basal Cell Carcinoma

NCT07251413 | Recruiting Phase 1

• 2 other identifiers: IOR-REG-25012025-520698-38-00
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

Basal cutaneous cell carcinoma (BCC) is the most common skin cancer. Early-stage disease is managed with surgery or radiation that cure more than 95% of patients. Surgical excision is the treatment of choice and by far the most convenient and effective means of achieving cure of any invasive BCC, Surgery is rarely contra-indicated even in old, debilitated patients, but in locally advanced tumors surgery has the potential of having functional and cosmetic consequences, due to a big tumor size or difficult locations and it is not uncommon tumors that are borderline for the indication of curative surgery. Patients with high-risk disease who have large primary lesions are usually not amenable to a definitive cure with local intervention and may experience significant morbidity, disfigurement, or functional deficits. In some patients, the tumors recur and progress locally being radiotherapy and Hedgehog inhibition therapy available options. Recently, cemiplimab was the first immunotherapy approved by the FDA and EMEA for locally advanced BCC after Hedgehog pathway inhibition The imiquimod (1-(2-methylpropyl)-1-H-imidazole \[4,5-c\] quinolone-amine) is a synthetic compound capable of activating the cells of the immune system, helping to control viruses, tumors, and intracellular parasites The combination of imiquimod plus anti PD-1 antibody could be synergistic. The main hypoteis is that combining cemiplimab, an immune checkpoint inhibitor targeting PD-1, and local treatment with the Toll-like receptor 7 (TLR7) agonist imiquimod may increase immune response against tumor and result in an increase in the rate of definitive cure y in patients with basal cell carcinoma (BCC) who have a high risk of recurrence after surgery alone or a high risk of morbidity, disfigurement, or functional deficits: to increase the rate of definitive cure. The CEMIQUID study main aims to evaluate:

1. 1.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.
2. 2.The antitumoral activity in terms of 3-years rate of relapse-free survival (RFS) according to RECIST 1.1 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.

Conditions

Cutaneous Basal Cell Carcinoma

Keywords

Cutaneous Carcinoma; Cemiplimab; Imiquimod; Laser Therapy

Outcome Measures

Primary Outcomes (2)

• Incidence adverse events (AE) and treatment-related AEs (TRAEs) assessed by NCI CTCAE v5.0

  The incidence of DLTs evaluated in Phase Ib: considered as the rate of patients who experience adverse events (AE) and treatment-related AEs (TRAEs) assessed by NCI CTCAE v5.0 which may be considered DLTs.

  During DLT evaluation period, the first 3 weeks of treatment for each patient

• Relapse-Free Survival (RFS) rate at 3 years.

  Relapse-Free Survival (RFS) rate at 3 years evaluated in Phase II study. 3-years RFS rate is defined as the percentage of patients free of locoregional progression or recurrence or new basocellular tumors, distant metastasis (RECIST v 1.1) or death due to any cause after 3 years from the date of study treatment. Patients not presenting any of the previous events will be censored at the date of last assessment. RFS will be summarized using the Kaplan-Meier method and displayed graphically where appropriate. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable. RFS will be calculated as median / mean (95% CI) for each cohort and RFS rate for different timepoints as applicable.The primary endpoint will be assessed locally and centrally. Central assessment will be prioritized for the primary endpoint.

  Throughout the study period, at 3 years from the start of treatment

Secondary Outcomes (6)

• Pathological response assessment

  Throughout the study period, at at 3 years from the start of treatment]

• Objective response rate (ORR)

  Throughout the study period, at 3 years from the start of treatment

• Clinical benefit rate (CBR)

  Throughout the study period, at at 3 years from the start of treatment

• Duration of clinical benefit (DBC)

  Throughout the study period, at at 3 years from the start of treatment

• Rate of resectability, and downstaging:

  Throughout the study period, at 6 months from the start of treatment

Study Arms (2)

Cohort 1: cemiplimab neoadjuvant treatment

ACTIVE COMPARATOR

Patients will be treated with single agent intravenous cemiplimab 350 mg every 3 weeks for a total of 4 neoadjuvant cycles (12 weeks).

Drug: cemiplimab

Cohort 2: cemiplimab plus topical imiquimod (plus fractional laser therapy) as neoadjuvant

EXPERIMENTAL

Patients will be treated with intravenous cemiplimab 350 mg every 3 weeks in combination with topical imiquimod 5% cream self-applied once daily 5 days per week (plus low-intensity laser therapy at 1- or 3-week interval), for a total of 4 neoadjuvant cycles (12 weeks).

Drug: cemiplimab; Drug: Topical imiquimod

Interventions

cemiplimab DRUG

cemiplimab 350 mg every 3 weeks for a total of 4 neoadjuvant cycles (12 weeks).

Cohort 1: cemiplimab neoadjuvant treatment; Cohort 2: cemiplimab plus topical imiquimod (plus fractional laser therapy) as neoadjuvant

Topical imiquimod DRUG

Topical imiquimod 5% cream self-applied once daily 5 days per week (plus low-intensity laser therapy at 1- or 3-week interval),

Cohort 2: cemiplimab plus topical imiquimod (plus fractional laser therapy) as neoadjuvant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed diagnosis of basal cell carcinoma (BCC), potentially resectable with curative intention.
• 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).
• Surgery would be recommended in routine clinical practice.
• Patient should be considered as high risk, defined as:
• at least 1 large lesion (≥ 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.
• Having basosquamous, infiltrative, sclerosing/morpheaform, micronodular, and BCC with carcinosarcomatous differentiation features in any portion of the tumor.
• 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.
• Multicentric tumors that would require a cosmetic disfigurement or functional defects by assessment of the enrolling physician will be eligible.
• At least one measurable lesion by RECIST v1.1 (Appendix 3).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Life expectancy of at least 24 weeks.
• 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.
• Adequate normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 x 109 cells/L

You may not qualify if:

• Distant metastatic disease (M1), visceral and/or distant nodal.
• Patients who have another malignancy that is progressing or requires active treatment, except:
• Non-melanoma skin cancer that has undergone potentially curative therapy In situ cervical carcinoma
• Any tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy).
• 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.
• 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.
• 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.
• 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.
• 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.
• Active tuberculosis.
• Receipt of a live vaccine within 28 days of enrollment.
• Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
• Recipient of a solid organ transplant (other than corneal transplants).

Sponsors & Collaborators

• Instituto Oncológico Dr Rosell: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (4)

Hospital Universitario Dexeus - Grupo Quirónsalud. Carrer de Sabino Arana, 19 Ed, Distrito de Les Corts

Barcelona, Barcelona, 08028, Spain

RECRUITING

Hospital Clínic de Barcelona. Carrer de Villarroel, 170, L'Eixample

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Ramón y Cajal. M-607, Km. 9, 100, Fuencarral-El Pardo,

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Miguel Servet de Zaragoza. P.º de Isabel la Católica, 1-3

Zaragoza, Zaragoza, 5009, Spain

RECRUITING

MeSH Terms

Interventions

cemiplimab; Imiquimod

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• María González Cao, M.D., Ph.D.

  Medical oncology Department / Dr Rosell Oncologic Institute. Hospital Dexeus, Barcelona, Spain

  STUDY CHAIR

• Susana Puig, M.D., Ph.D.

  Hospital Clinic of Barcelona

  STUDY CHAIR

Central Study Contacts

Federico Nepote

CONTACT

+34 93 434 44 12; investigacion@mfar.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: CEMIQUID is a multi-center, open-label, phase Ib/II, two-cohort study for patients with high risk, potentially resectable basal cell carcinoma (BCC). Patients enrolled in the Phase II part of the study will be randomly assigned to Cemiplimab +/- Imiquimod The study is divided into two phases: Phase Ib: 6 patients will be included and the main objective will be 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. Phase II: If the treatment is deemed feasible on Phase Ib, 12 additional patients will be included 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 re

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: November 26, 2025
• Study Start: October 22, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)