Anti-PD1-antibody and Pulsed HHI for Advanced BCC

NCT04679480 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: SGZ-2018-12355
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the tumour response, safety and induction of immune response in patients with advanced BCC treated with a combination of anti-PD1 antibody and pulsed hedgehog inhibitor.

Conditions

Basal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best response any time between the treatment start and 26 weeks after the initiation of the treatment.

  The response will be assessed according to the Immune-response Criteria (Appendix) in all patients with cutaneous lesions as: complete response, partial response, stable disease or progressive disease. The best response documented between treatment start and week 26 will be considered "best response". In case of metastatic BCC without cutaneous lesions at screening, the primary outcome will be assessed using PET/CT imaging according to the PERCIST criteria every 12 weeks from treatment start. In patient withdrawn from the trial before week 26, the last tumour assessment will be used for evaluation of primary outcome. For patients withdrawn from the study a full body physical examination and laboratory results will be performed prior to withdrawal, unless refused by the patient.

  At baseline, each assessment and the week 26.

Secondary Outcomes (3)

• Tumour response at 26 weeks after the initiation of the treatment

  26 weeks after the initiation of the treatment

• Detection of histologic changes in the tumour in patients with biopsy-assessable tumours

  Histologic changes will be compared in the biopsies taken at baseline, week 2, week 26, and, if applicable, week 4 and week 12.

• Evaluation of the changes in immunogenicity of the tumour and tumour microenvironment in patients with biopsy-assessable tumours

  Immunogenicity will be compared in the biopsies taken at baseline, week 2, week 26, and, if applicable, week 4 and week 12.

Study Arms (1)

Intervention

EXPERIMENTAL

Investigational product: a combination of an anti-PD1 antibody (Cemiplimab) and a HHI (Sonidegib). Cemiplimab will be supplied as a liquid in a sterile, single-use 10 ml vial. Each vial will contain a volume of 7ml at a concentration of 50mg/ml. Cemiplimab will be prepared for infusion at the trial site and administered as a flat 350mg dose in 100ml sodium chloride 0.9% as an IV infusion over approximately 30 minutes (±10 minutes) in an outpatient setting. Each patient's dose will be administered as a flat 350mg dose in every 3 weeks, starting from week 2 of the trial. The Hedgehog Inhibitor used for the trial will be Sonidegib. Sonidegib is a white 200mg capsule, orally administered once daily. Sonidegib will be administered in a 2 week cycle every 4 weeks (pulsed therapy: 2 weeks on, 2 weeks off), starting from week 0 of the trial.

Drug: Cemiplimab Injection [Libtayo]

Interventions

Cemiplimab Injection [Libtayo] DRUG

Investigational product: a combination of an anti-PD1 antibody (Cemiplimab) and a HHI (Sonidegib). Cemiplimab will be supplied as a liquid in a sterile, single-use 10 ml vial. Each vial will contain a volume of 7ml at a concentration of 50mg/ml. Cemiplimab will be prepared for infusion (as described in SmPC (Fachinformation Swissmedic) Libtayo, see Appendix) at the trial site and administered as a flat 350mg dose in 100ml NaCl 0.9% as an IV infusion over approximately 30 minutes (±10 minutes) in an outpatient setting. Each patient's dose will be administered as a flat 350mg dose in every 3 weeks, starting from week 2 of the trial. The Hedgehog Inhibitor used for the trial will be Sonidegib. Sonidegib is a white 200mg capsule, orally administered once daily. Sonidegib will be administered in a 2 week cycle every 4 weeks (pulsed therapy: 2 weeks on, 2 weeks off), starting from week 0 of the trial.

Also known as: Sonidegib

Intervention

Eligibility Criteria

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

You may qualify if:

• Informed Consent as documented by signature
• Histologically or cytologically confirmed advanced BCC, defined as: a) metastasized BCC, b) locally advanced BCC, not suitable for surgical or radio-therapeutic treatment c) multiple BCCs (\>5) d) BCC \>10mm; not suitable for surgery or radiotherapy
• Subjects must have an evaluable disease as measured by Immune-related Response criteria, or PERSIST (PET response criteria in solid tumours) criteria in patients with metastatic BCCs without cutaneous lesions.
• Subjects (males and females) aged ≥ 18 years
• Adequate organ function (hematologic, renal, hepatic), as assessed by the study physician. Deviations of the following parameters are allowed upon decision of the investigator in case that these are not considered to be of clinical relevance and/or don't represent organ dysfunction or correspond to allowed comorbidities as specified in section 7.1:
• Absolute neutrophil count \>1.5 x 109/l
• Hemoglobin \>9 g/dL
• Platelets ≥ 100 x 109/l
• Serum total bilirubin \<1.5 x Upper limit of normal (ULN) (or ≤3x ULN, if liver metastases).
• Alanine transaminase (ALT) and Aspartate transaminase (AST) \< 3 x ULN or \<5 ULN if liver metastases are present
• Patients with Gilbert's Disease and total bilirubin up to 3x ULN may be eligible after communication with and approval from the medical monitor
• Alkaline phosphatase (ALP) ≤2.5x ULN (or ≤5x ULN, if liver or bone metastases)
• Serum creatinine \< 2 x ULN
• Creatine phosphokinase (CPK) (also known as creatine kinase (CK)) elevation ≤ grade 2
• Eastern Cooperative Oncology Group (ECOG) ≤2

You may not qualify if:

• History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
• Patients with allergy or hypersensitivity to Cemiplimab or to any of the excipients of Libtayo. Specifically, because of the presence of trace components in Cemiplimab, patients with allergy or hypersensitivity to doxycycline or tetracycline are excluded.
• Patients with allergy or hypersensitivity to Sonidegib or to any of the excipients of Odomzo.
• Patients with a history of solid organ transplant (patients with prior corneal transplants may be allowed to enrol after discussion with and approval from the medical monitor)
• Receipt of live vaccines (including attenuated) within 30 days of first study treatment or patient unwilling not to receive them during the treatment and for up to 5 half-lives after the last dose of Cemiplimab
• Known of suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study, due to language problems, psychological disorders, social conditions or dementia
• Currently receiving treatment with another investigational device or study drug, or \<28 days since ending treatment with another investigational device or study drug
• Any anticancer treatment other than radiation therapy (chemotherapy, targeted systemic therapy, imiquimod, photodynamic therapy), investigational or standard of care, within 30 days of the initial administration of Cemiplimab or planned to occur during the study period
• Prior treatment with an agent that blocks the PD-1/PD-L1 pathway
• Female subject is pregnant or breast-feeding, or planning to become pregnant or breast-feed, or unwilling to use acceptable method(s) of effective contraception during study treatment and during 20 months after the last dose of Sonidegib; and during 6 months (4 in case of breast-feeding) after the last dose of Cemiplimab in case of a Cemiplimab monotherapy (in case of continuation of treatment as detailed in section 6.1)
• Male subject is planning to procreate, donate Semen, or unwilling to use acceptable method(s) of effective contraception during study treatment and during 6 months after the last dose of Sonidegib or Cemiplimab
• Subject is unwilling to renounce to blood spending during the treatment and during 20 months after the last dose of Sonidegib.
• Subject is unwilling to renounce to any elective surgery during the treatment period and for at least 30 days after the administration of the study drug
• Impaired cardiac function or clinically significant heart disease, including any of the following:

Sponsors & Collaborators

• Reinhard Dummer: lead
• Sanofi: collaborator
• Sun Pharmaceutical Industries Ltd: collaborator

Study Sites (1)

University Hospital Zurich, Clinic of Dermatology

Zurich, 8058, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Basal Cell

Interventions

cemiplimab; sonidegib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell

Study Officials

• Reinhard Dummer, Prof.

  University Hospital Zurich, Clinic of Dermatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 22, 2020
• Study Start: February 18, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: July 30, 2024

Record last verified: 2024-07

Locations

CH (1)