Nivolumab for Treatment of Squamous Cell Carcinoma of the Skin

NCT04204837 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CA209-587
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 7

Brief Summary

To determine the Objective Response Rate (ORR) of immunotherapy with Nivolumab (Group 1) and Nivolumab plus Relatlimab (Group 2) in patients with locally advanced/metastatic squamous cell carcinoma of the skin using Response Criteria in Solid Tumors Version 1.1 (RECIST1.1) per site assessment (Time Frame Group 2: From first dose up to 5 years)

Conditions

Squamous Cell Carcinoma of the Skin

Keywords

Nivolumab; Relatlimab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  using Response Criteria in Solid Tumors Version 1.1 (RECIST1.1) per site assessment

  up to 5 years

Secondary Outcomes (7)

• Disease Control Rate (DCR)

  up to 5 years

• Duration of Response (DOR) in patients who achieve partial response (PR) or better

  up to 5 years

• Progression Free Survival (PFS)

  up to 5 years

• Overall Survival (OS)

  up to 5 years

• ORR and DCR for patients with PD-L1-positive tumor expression and/or positive LAG-3 expression of tumor-infiltrating cells

  up to 5 years

Study Arms (2)

Nivolumab

EXPERIMENTAL

Nivolumab will be given on Day 1 of every 14-day cycle (Q2W) at a dose of 240 mg as an IV infusion until progression, unacceptable toxicity or discontinuation for other reasons for up to 2 years.

Drug: Nivolumab

Nivolumab plus Relatlimab

EXPERIMENTAL

Patients wil receive a fixed-dose combination of nivolumab 480 mg and relatlimab 160 mg by intravenous infusion every four weeks (Q4W) (Group 2) for up to two years after initial dosing or until PD - or absence of investigator-assessed clinical benefit

Drug: Nivolumab plus Relatlimab

Interventions

Nivolumab DRUG

Nivolumab will be given on Day 1 of every 14-day cycle (Q2W) at a dose of 240 mg as an IV infusion until progression, unacceptable toxicity or discontinuation for other reasons for up to 2 years.

Nivolumab

Nivolumab plus Relatlimab DRUG

Patients wil receive a fixed-dose combination of nivolumab 480 mg and relatlimab 160 mg by intravenous infusion every four weeks (Q4W) (Group 2) for up to two years after initial dosing or until PD - or absence of investigator-assessed clinical benefit

Nivolumab plus Relatlimab

Eligibility Criteria

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

You may qualify if:

• Men and women, 18 years of age and older on day of signing written informed consent
• Histologically or cytologically documented locally-advanced and/or metastatic squamous cell carcinoma of the skin (stage III/IV AJCC 2010) that is incurable
• Archival tumor tissue available for evaluation of PD-L1 and LAG-3 expression
• Measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration:
• WBC ≥ 2000/μl
• Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x103/μL
• Hemoglobin \> 9.0 g/dL
• 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
• AST/ALT ≤ 3 x ULN
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)

You may not qualify if:

• 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
• Prior therapy with CTLA-4, PD-1 or LAG-3 antibodies
• History of myocarditis, regardless of etiology
• Troponin T (TnT) or I (TnI) \> 2× institutional upper limit of normal (ULN). Participants with TnT or TnI levels between \> 1× to 2× ULN will be permitted if repeat levels within 24 hours are ≤ 1× ULN. If TnT or TnI levels are between \> 1× to 2× ULN within 24 hours, 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 \< 2× ULN, the participant may undergo a cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the Investigator
• A condition requiring systemic treatment with either corticosteroids (\> 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
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• 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
• Patients with serious intercurrent illness, requiring hospitalization
• Other serious illnesses, e.g. serious infections requiring antibiotics
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Pregnancy (absence to be confirmed by ß-HCG urinary test, minimum sensitivity 25 IU/L or equivalent units of HCG)) or lactation period
• Women of childbearing potential (WOCBP): Refusal or inability to use effective means of contraception (Pearl-Index \<1)
• History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• 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

Sponsors & Collaborators

• Salzburger Landeskliniken: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Universitätsklinikum Graz - LKH, Klinische Abteilung für Onkologie

Graz, 8020, Austria

RECRUITING

LKH Innsbruck Universitätsklinik für Dermatologie und Venerologie

Innsbruck, 6020, Austria

RECRUITING

Klinikum Klagenfurt am Wörthersee

Klagenfurt, 9020, Austria

COMPLETED

Universitätsklinik für Dermatologie und Allergologie der Paracelsus medizinischen Privatuniversität Salzburg

Salzburg, 5020, Austria

RECRUITING

Abteilung für Haut- und Geschlechtskrankheiten, Universitätsklinikum St. Pölten Karl Landsteiner Privatuniversität für Gesundheitswissenschaften

Sankt Pölten, 3100, Austria

RECRUITING

Med Uni Wien, Univ. Klinik für Dermatologie

Vienna, 1090, Austria

RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, 4600, Austria

RECRUITING

MeSH Terms

Interventions

Nivolumab; relatlimab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Martin Laimer, MD

  Salzburger Landeskliniken

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Laimer, MD

CONTACT

+4357255; m.laimer@salk.at

Roland Lang, PhD

CONTACT

+4357255; r.lang@sak.at

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: a.o. Univ.-Prof. Dr. med. univ., MSc

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 19, 2019
• Study Start: March 6, 2017
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

AU (7)