A Prospective, Open, Single-arm, Single Center, Phase II Trial to Assess the Efficacy of Anti-PD1 Antibody in Combination With Pulsed Hedgehog Inhibitor in Advanced Basal Cell Carcinoma.
Overview
- Phase
- Phase 2
- Intervention
- Cemiplimab Injection [Libtayo]
- Conditions
- Basal Cell Carcinoma
- Sponsor
- Reinhard Dummer
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Best response any time between the treatment start and 26 weeks after the initiation of the treatment.
- Status
- Active, Not Recruiting
- Last Updated
- last year
Overview
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.
Detailed Description
A prospective, open, single-arm, single center, phase II trial to assess the efficacy of anti-PD1 antibody in combination with pulsed Hedgehog inhibitor in advanced Basal Cell Carcinoma. 20 patients with advanced BCC will be included in the trial. No blinding or randomization will be conducted in this open label, non-randomized clinical trial. All of the patients will receive the investigative treatment (combination of anti-PD1 antibody and pulsed HHI therapy). The tumor response will be evaluated comparing tumour size at baseline, at each assessment, and 26 weeks after treatment initiation. The study duration from screening visit to the End of Study visit is 32 weeks with a Follow-Up 1 Visit at week 28 and Follow-Up 2 Visit at week 32. The duration of the translational part (secondary objectives) of the study is up to 24 months. If the best response any time at week 26 is partial response, patients will be offered to continue at least one of the study drugs until complete response or until a maximum of 2 years. The evaluation during this period will correspond to the standard of care with laboratory tests at each follow up and imaging every 12 weeks.
Investigators
Reinhard Dummer
Prof. Dr. med
University of Zurich
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Intervention
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.
Intervention: Cemiplimab Injection [Libtayo]
Outcomes
Primary Outcomes
Best response any time between the treatment start and 26 weeks after the initiation of the treatment.
Time Frame: At baseline, each assessment and the week 26.
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.
Secondary Outcomes
- 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.)
- 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.)