Locally Advanced/Metastatic Squamous Cell Carcinoma of the Skin
Conditions
Interventions
Trade Name: Opdivo (100 mg / 10 ml)
Product Name: Nivolumab
Product Code: BMS-936558-01
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Nivolumab
CAS Number: 946414-94-4
Curr
Sponsors
Universitätsklinik für Dermatologie und Allergologie der Paracelsus medizinischen Privatuniversität Salzburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women, 18 years of age and older on day of signing written informed consent 2. Histologically or cytologically documented locally-advanced and/or metastatic squamous cell carcinoma of the skin (stage III/IV AJCC 2010) that is incurable 3. Archival tumor tissue available for evaluation of PD-L1 and LAG-3 expression 4. Measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 5. Life expectancy of at least 12 weeks 6. Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2 7. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration: o WBC = 2000/µl o Neutrophils = 1500/µL o Platelets = 100 x103/µL o Hemoglobin > 9.0 g/dL o Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140- age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL o AST/ALT = 3 x ULN o Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 41
Exclusion criteria
Exclusion criteria: 1. Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment 2. Prior therapy with CTLA-4, PD-1 or LAG-3 antibodies 3. History of myocarditis, regardless of etiology 4. Troponin T (TnT) or I (TnI) >2x institutional upper limit of normal (ULN). Participants with TnT or TnI levels between >1x to 2x ULN will be permitted if repeat levels within 24 hours are 1x to 2x ULN within 24 hous, the participant may undergo a cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the Investigator. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease 6. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis 7. Known additional malignancy that is progressing or requires active treatment. Patients with chronic lymphocytic leukemia that is stable under active therapy are eligible for inclusion. 8. An active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger 9. Patients with serious intercurrent illness, requiring hospitalization 10. Other serious illnesses, e.g. serious infections requiring antibiotics or hospitalization 11. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial 12. Pregnancy (absence to be confirmed by ß-HCG urinary test, minimum sensitivity 25 IU/L or equivalent units of HCG)) or lactation period 13. Women of childbearing potential (WOCBP): Refusal or inability to use effective means of contraception (Pearl-Index <1) 14. History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) 15. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection 16. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator 17. Known hypersensitivity reaction to any of the components of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the Objective Response Rate (ORR) of immunotherapy with Nivolumab (Group 1) and Nivolumab plus Relatlimab (Group 2) in patients with locally advanced/metastativ squamous cell carcinoma of the skin using Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) per site assessment (Time Frame Group 2: From first dose up to 5 years);Secondary Objective: - Disease Control Rate (DCR) using Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) per site assessment (Time Frame Group 2: From first dose to date of first documented tumor progression or death, whichever comes first (up to 5 years)) - Duration of Response (DOR) in patients who achieve partial response (PR) or better (Time Frame Group 2: From time of documented PR or better to date of first documented tumor progression or death, whichever comes first (up to 5 years)) - Progression Free Survival (PFS) (Time Frame Group 2: From first dose to date of first documented tumor progression or death, whichever comes first (up to 5 years)) - Overall Survival (OS) (Time Frame: From first dose to the date of death due to any cause (up to 5 years)) - ORR, DCR, DOR, PFS and OS for patients with PD-L1-positive tumor expression (>1% positive tumor cells) and/or positive LAG-3 expression (i.e. >1% positive tumor infiltrating cells) - Safety and toxicity of Nivolumab plus Relatlimab;Primary end point(s): To determine the Objective Response Rate (ORR) of immunotherapy with Nivolumab (Group 1) and Nivolumab plus Relatlimab (Group 2) in patients with locally advanced/metastativ squamous cell carcinoma of the skin using Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) per site assessment (Time Frame Group 2: From first dose up to 5 years);Timepoint(s) of evaluation of this end point: 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Disease Control Rate (DCR) using Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) per site assessment (Time Frame (Group 2): from first dose to date of first documented tumor progression or death, whichever comes first (up to 5 years)) - Duration of Response (DOR) in patients who achieve partial response (PR) or better (Time Frame (Group 2): from date of documented PR or better to date of first documented tumor progression or death, whichever comes first (up to 5 years)) - Progression Free Survival (PFS) (Time Frame (Group 2): From first dose to date of first documented tumor progression or death, whichever comes first (up to 5 years)) - Overall Survival (OS) (Time Frame: From first dose to the date of death due to any cause (up to 5 years)) - ORR, DCR, DOR, PFS and OS for patients with PD-L1-positive tumor expression (>1% positive tumor cells) and/or positive LAG-3 expression (i.e. >1% positive tumor-infiltrationg cells) - Safety and toxicity of Nivolumab plus Relatlimab (Group 2);Timepoint(s) of evaluation of this end point: 5 years | — |
Countries
Austria
Contacts
Public Contacta.o. Univ. Prof. Dr. Martin Laimer
Univ.klinik f. Dermatologie u. Allergologie der Paracelsus Medizinischen Privatuniversität Salzburg
Outcome results
None listed