The disease under clinical investigation is represented by resectable Merkel Cell Carcinoma (MCC), stage IIA-III (according to the AJCC staging system 8th edition). The study will include patients with a disease amenable for radical surgery as defined by local or institutional surgical practices, based on multidisciplinary team assessment MedDRA version: 21.1 Level: LLT Classification code 10064025 Term: Merkel cell carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: RETIFANLIMAB
Product Code: [INCMGA00012]
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 2079108-44-2
Current Sponsor code: RETIFANLIMAB
Other descriptive name: Re
Sponsors
Fondazione GONO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all the following criteria apply: 1. Signed informed consent. 2. Subjects must be 18 years old or older. 3. ECOG performance status of 0 to 1. 4. Histologically confirmed diagnosis of MCC amenable for radical surgery as defined by local or institutional surgical practices, based on multidisciplinary team assessment. Subjects must have one of the following stages of disease: a. Stage IIA - IIB- III (according to the AJCC staging system 8th edition) b. Local/Regional recurrent disease after primary surgery, as defined as total disease burden = 1 cm diameter amenable for a radical intent surgery. Note: nodal disease without any known primary (in absence of a primary cutaneous site after a complete diagnostic/staging work-up including chest/abdomen CT-scan, dermatologic clinical examination and 18F-FDG-PET scan) can be enrolled and will be considered as Stage III. 5. Able to provide archival FFPE tumor samples (if collected within three months from study enrollment) or have a tumor amenable to pre-treatment biopsy. Excisional, incisional, or core-needle samples are acceptable. Fine needle aspirates are not allowed. 6. No prior systemic treatment or neoadjuvant radiation therapy. 7. Adequate bone marrow function characterized by the following at screening: 4. Platelets = 100 × 109/L 5. Absolute neutrophil count (ANC) =1.5 x 109/L 6. Hemoglobin = 9.0 g/dL 8. Adequate renal function characterized by serum creatinine = 1.5 × upper limit of normal (ULN) OR calculated by Cockroft-Gault formula or directly measured creatinine clearance = 60 mL/min at screening for subject receiving cisplatin OR creatinine clearance = 50 mL/min at screening for subject receiving carboplatin. 9. Adequate hepatic function characterized by the following at screening: c. Serum total bilirubin = 1.5 × ULN and =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1.Prior systemic therapy for MCC, including chemotherapy and prior PD-1 or PD-L1-directed therapy. 2.Primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine 3.Treatment with anticancer drugs, radiation therapy or participation in another interventional clinical study within 28 days before the first administration of study drug 4.Distant metastases at any site 5.Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry except for cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer or other noninvasive or indolent malignancy 6.Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: a.History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft [CABG], coronary angioplasty or stenting) = 6 months prior to start of study treatment; b.Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality = 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia 7.History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis Note: Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Subjects with controlled type I diabetes mellitus on a stable insulin regimen, vitiligo or psoriasis not requiring systemic treatment may be eligible 8.History of chronic conditions (i.e. COPD) requiring systemic immune-suppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent) 9.Evidence of interstitial lung disease or active noninfectious pneumonitis 10.History of organ transplant, including allogeneic stem cell transplantation 11.History or current evidence of any condition, therapy or laboratory abnormality that might interfere with the subject’s participation to the study or is not in the best interest of the subject to participate, in the opinion of the treating investigator 12.Know active hepatitis B [positive HBV surface antigen (HBsAg) result] or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA 13.Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per µL or more; HIV viral load must be undetectable per standard of care assay, and they have to be compliant with antiretroviral treatment 14.Active infections requiring systemic therapy, or systemic antibiotic use up to 28 days before C1D1 15.Live vaccines within 28 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the activity of the one cycle of preoperative retifanlimab plus platinum-etoposide chemo-immunotherapy regimen as measured in terms of pathological complete response (pCR).;Secondary Objective: To assess the safety and tolerability of the study regimen and to describe the surgical procedures’ morbidity. To assess the impact of the study regimen on patients’ quality of life. To perform tumor tissue spatial profiling of matched pre- and post-treatment samples to uncover changes. To perform ultra-deep sequencing of circulating tumor DNAin liquid biopsies to track ctDNA clearance, lack of detectable minimal residual disease and treatment resistance mechanisms. To assess the association of tumor Merkel cell polyomavirus status, immune checkpoints expression and Tumor Mutational Burden with the activity of the study regimen. To assess the relapse-free survival. To assess the overall survival. To obtain sperimental models To perform radiomic analyses for predicting the presence of tumor heterogeneity at baseline and the pCR status achieved by the study regimen. To analyze microbiota to evaluate the existence of a prognostic/predictive immune signature.;Primary end point(s): The study primary endpoint will be the pathological complete response rate or pCR rate, defined as the percentage of patients, relative to the total of enrolled subjects in the intention-to-treat population, who will achieve a pathological complete response, as per central pathological review. Pathological complete response will be defined as the absence of residual viable invasive cancer on evaluation of the complete resected tumor specimen and all sampled regional lymph nodes.;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Treatment safety defined (incidence of AE during the preoperative study regimen, assessed according to National Cancer Institute Common Toxicity Criteria version 5.0. Patient Reported Outcomes (PROs) assessed by the completion of quality-of-life questionnaires, FACT-M Questionnaire and EQ-5D-5L. Assessment of tumor/microenvironmental changes induced (via gene expression profiles of cancer cells, lymphocytes, and macrophages). Correlation of pCR with ctDNA mutational profiles and its clearance after the preoperative study treatment. Correlation of tumor Merkel cell polyomavirus (MCPyV) status and PD-L1 expression of with the activity of the preoperative study regimen. Relapse Free Survival. Overall survival.;Timepoint(s) of evaluation of this end point: Quality of life and safety: 24 months Survival and traslational endpoints: 48 months | — |
Countries
Italy
Contacts
Public ContactUfficio Sperimentazioni sede operat
Fondazione GONO Onlus
Outcome results
None listed