P3.02c-038 First-Line Atezolizumab plus Chemotherapy in Chemotherapy-Naïve Patients with Advanced NSCLC: A Phase III Clinical Program: Topic: IT

Abstract

First-line treatments for patients with advanced NSCLC include targeted therapies and platinum-based doublet chemotherapy±bevacizumab and/or pemetrexed. Although immunotherapies targeting the PD-L1/PD-1 pathway are available for advanced NSCLC beyond the first line, chemotherapy is a key first-line option for patients, despite poor survival outcomes, highlighting the need for additional treatment options. Atezolizumab, a monoclonal anti–PD-L1 antibody, inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, restoring tumor-specific T-cell immunity. Clinical efficacy has been reported with atezolizumab monotherapy in patients with squamous and nonsquamous NSCLC, with a survival benefit observed across all PD-L1 expression levels. Additionally, Phase Ib data showed the potential for chemotherapy to further enhance responses to atezolizumab, with tolerable safety, in patients with NSCLC. Bevacizumab in combination with atezolizumab may enhance efficacy in non-squamous NSCLC by inhibiting VEGF-mediated immunosuppression. Four global, Phase III, randomized, open-label trials are evaluating atezolizumab+platinum-based chemotherapy±bevacizumab in chemotherapy-naive patients with stage IV NSCLC. Eligible patients must have stage IV NSCLC, measurable disease (RECIST v1.1) and ECOG PS 0-1 and be chemotherapy naive. Exclusion criteria include untreated CNS metastases, autoimmune disease and prior exposure to immunotherapy. Patients will be enrolled regardless of PD-L1 expression status. Patients randomized to the experimental arm will receive atezolizumab 1200 mg with standard platinum-based chemotherapy in IMpower130 and 131 and also ±bevacizumab in IMpower150 for four or six 21-day cycles, then maintenance with atezolizumab in IMpower130 and 131 and atezolizumab+bevacizumab in IMpower150. In IMpower132, experimental-arm patients will receive atezolizumab+platinum-based chemotherapy+pemetrexed, then maintenance with atezolizumab+pemetrexed. Patients receiving atezolizumab may continue until loss of clinical benefit. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include objective response rate and safety. Evaluation of predictive biomarkers associated with efficacy will be performed.Tabled 1TrialIMpower130IMpower131IMpower132IMpower150HistologyNonsquamousSquamousNonsquamousNonsquamousPlanned enrollment(N)65010255681200ExperimentalAtezolizuma+carboplatin+nab-paclitaxelAtezolizuma+carboplatin+paclitaxel or Atezolizumab+carboplatin+nab-paclitaxelAtezolizuma+carboplatinor cisplatin+pemetrexedAtezolizumab+carboplatin+paclitaxel or Atezolizumab+carboplatin+paclitaxel+bevacizumabComparatorCarboplatin+nab-paclitaxelCarboplatin+nab-paclitaxelCarboplatinor cisplatin+pemetrexedCarboplatin+paclitaxel+bevacizumabStratification factorsSexLiver metastasesCentrally assessedPD-L1 expression by IHCSexLiver metastasesCentrally assessedPD-L1 expression by IHCSexECOG PSChemotherapy type (carboplatin vs cisplatin)Smoking statusSexLiver metastasesCentrally assessedPD-L1 expression by IHCIdentifierNCT02367781NCT02367794NCT02657434NCT02366143ECOG PS, Eastern Cooperative Oncology Group performance status; IHC, immunohistochemistry. Open table in a new tab ECOG PS, Eastern Cooperative Oncology Group performance status; IHC, immunohistochemistry. Section not applicable. Section not applicable.