study of novel treatment combinations in patients with lung cancer

Conditions: Lung Cancer; Advanced or Metastatic Non-Small-Cell Lung Cancer; Resectable Non-Small-Cell Lung Cancer

Summary: the goal of this platform clinical trial is to test how well novel treatment combinations work in participants with lung cancer. substudy-01 will compare the different novel combinations versus standard of care in participants with metastatic (cancer that has spread) non-small-cell lung cancer (nsclc) who have not been treated before. substudy-02 will compare the different novel combination versus standard of care in participants with cancer that has progressed after receiving previous treatment for metastatic nsclc. substudy-03 will compare the different novel combinations versus standard of care in participants with resectable stage ii-iii nsclc. the primary objectives of this study are: substudy-01 and substudy-02: to evaluate the objective response rate (orr) assessed per response evaluation criteria in solid tumors version 1.1 (recist v1.1). substudy-03: to evaluate the efficacy of treatment combinations based on complete pathological response (pcr) rate.


Eligibility criteria:
key inclusion criteria: all substudies: * histologically or cytologically documented non-small-cell lung cancer (nsclc). * no known actionable genomic alterations for which targeted therapies are available. * eastern cooperative oncology group (ecog) performance status score of 0 or 1. * measurable disease per response evaluation criteria in solid tumors. * adequate hematologic and end-organ function. * individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception. substudy 01: all experimental arms * stage iv nsclc. * for individuals with nonsquamous histology: epidermal growth factor receptor (egfr) or anaplastic lymphoma kinase (alk) alteration negative. * pd-l1 status by central confirmation. * no prior systemic treatment for metastatic nsclc. substudy 02: all experimental arms * stage iv nsclc. * in individuals with nonsquamous histology and actionable egfr, alk, or other known genomic alterations must have received treatment with at least 1 targeted therapy to the appropriate genomic alteration. substudy 03: all experimental arms * previously untreated individuals with resectable (stage ii, iiia, iiib (t\[3-4\]n2) nsclc (per american joint committee on cancer (ajcc) edition 8). * planned surgery must comprise of lobectomy, sleeve lobectomy, or bi-lobectomy. * pd-l1 status by central confirmation. * for individuals with nonsquamous histology: epidermal growth factor receptor (egfr) or anaplastic lymphoma kinase (alk) alteration negative. key exclusion criteria: all substudies: * mixed small-cell lung cancer and nsclc histology. * active second malignancy. * active autoimmune disease. * history of or current non-infectious pneumonitis/interstitial lung disease. * active serious infection within 4 weeks prior to study treatment. substudy 01 and 02 * known active central nervous system (cns) metastases and/or carcinomatous meningitis. * received previous anticancer therapy within 4 weeks prior to enrollment. substudy 03: all experimental arms * nsclc previously treated with systemic therapy or radiotherapy. * received prior treatment with any anti-pd-(l)-1 or other immune checkpoint inhibitors (cpis). note: other protocol defined inclusion/exclusion criteria may apply