CEMIPLIMAB for Basal cell carcinoma

Inclusion criteria

• {"criterion_text":"- 1. Male/female participants who are at least 18 years of age on the day of signing informed consent.\n- 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.\n- 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.\n- 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.\n- 4. At least one measurable lesion by RECIST v1.1 (Appendix 3).\n- 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n- 6. Life expectancy of at least 24 weeks.\n- 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.\n- 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\n- 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."}

Exclusion criteria

• {"criterion_text":"- 1. Distant metastatic disease (M1), visceral and/or distant nodal.\n- 10. Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.\n- 11. Recipient of a solid organ transplant (other than corneal transplants).\n- 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.\n- 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.\n- 14. Has participated in a study of an investigational agent or an investigational device within 4 weeks of enrollment.\n- 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.\n- 16. Female patients who are pregnant or breast-feeding.\n- 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).\n- 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.\n- 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.\n- 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.\n- 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.\n- 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.\n- 8. Active tuberculosis.\n- 9. Receipt of a live vaccine within 28 days of enrollment."}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Assessed by NCI CTCAE v5.0 (Appendix 5)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Defined as proportion of patients free of locoregional progression/recurrence, distant metastasis (per RECIST v1.1) or death from any cause at 3 years from study treatment initiation."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Pathologic complete response (pCR) per Immune-Related Pathologic Response Criteria (irPRC): 0% residual viable tumor in post-therapy surgical specimen (Appendix 4)."}
• {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Clinical benefit rate (CBR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of clinical benefit (DBC)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Relapse-free survival (RFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II: ● Pathologic complete response (pCR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Clinical benefit rate (CBR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of clinical benefit (DBC)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rate of resectability, downstaging","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Adverse events (AE)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Treatment-related AEs (TRAEs)","definition_or_measurement_approach":""}

Spain

Earliest CTIS Part Ii Submission Date

13-06-2025

Latest Decision Or Authorization Date

16-07-2025

Processing Time Days

33

Number Of Sites

4

Number Of Participants

18

Primary sponsor

Full Name

Instituto Oncologico Dr. Rosell S.L.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain