Skyscraper-01/GO41717: A phase III, randomized, double-blinded, placebo-controlled study of tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab compared with placebo in combination with atezolizumab in patients with previously untreated locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer
Indication :

cancer du poumon non à petites cellules non traité de stade avancé inopérable ou métastatique


Sponsor :

ROCHE


Phase :

III


Ligne :

première


Traitement :

tiragolumab ou placebo + atezolizumab


Spécificités :

cancer du poumon non à petites cellules non traité de stade avancé inopérable ou métastatique


Site :

CHUV


Contact(s) :
Solange Peters
Investigateur principal

CHUV
Département d'Oncologie - Service d'oncologie médicale

Rue du Bugnon 46
Lausanne
1011

+41795560192
solange.peters@chuv.ch

Primary objective :

L’objectif de cette étude clinique est de comparer les effets positifs et négatifs de l’association tiragolumab plus atezolizumab chez des patients atteints de CPNPC à ceux de l’association placebo plus atezolizumab.


Inclusion criteria :
  • Age >/= 18 years at time of signing Informed Consent Form
  • ECOG Performance Status of 0 or 1
  • Histologically or cytologically documented locally advanced or recurrent NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic Stage IV NSCLC of either squamous or non-squamous histology
  • No prior systemic treatment for metastatic NSCLC
  • Tumor PD-L1 expression with a TPS >/= 50%
  • Measurable disease per RECIST v1.1
  • Life expectancy >= 12 weeks
  • Adequate hematologic and end-organ function
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  • Negative HIV test at screening
  • Negative hepatitis B surface antigen (HBsAg) test at screening
  • Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion criteria :
  • Patients with non-squamous NSCLC who have an unknown EGFR or ALK status will be required to be tested at prescreening or screening.
  • Patients with squamous NSCLC who have an unknown EGFR or ALK status are eligible and will not be required to be tested at pre-screening/screening.
  • Pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >/= 2 weeks prior to screening
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled or symptomatic hypercalcemia
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Active tuberculosis
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease, or current alcohol abuse
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
  • History of malignancy other than NSCLC within 5 years prior to screening
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • Prior allogeneic stem cell or solid organ transplantation
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the
    interpretation of the results, or may render the patient at high risk from treatment complications
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
  • Current treatment with anti-viral therapy for HBV or HCV
  • Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tiragolumab or atezolizumab formulation
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
  • Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to randomization.