LBA2 Phase II study of PD-L1 expression guidance on neoadjuvant (NA) nivolumab (Nivo) monotherapy with or without platinum-doublet chemotherapy in resectable NSCLC

BackgroundWe profiled clinical and biomarker data from this prospective, multicenter, phase II study evaluating the efficacy and safety of NA nivo with or without platinum-doublet chemotherapy based on PD-L1 status (NCT04015778).MethodsPatients (pts) had resectable clinical stage IIA-IIIB (AJCC 8th) NSCLC and ECOG PS 0/1 with no EGFR/ALK variations. Pts received mono-nivo 360mg treatment (tx) for ≤3 cycles q3w or nivo 360mg + nab-paclitaxel 185mg/m2 (d1, d8) + carboplatin AUC5 for ≤3 cycles q3w based on PD-L1 status. Primary endpoint was major pathological response (MPR: ≤10% viable tumor cells). Key secondary endpoints included pathologic complete response (pCR), objective response rate (ORR, RECIST v1.1), adverse events (AEs) including treatment-related (TRAE) and immune-related (irAE). We correlated PD-L1 status and perioperative ctDNA presence with pCR and event-free survival (EFS).ResultsTable: LBA2ParameterA1A2B1B2SumEnrolled1212161252PD-L1≥ 50%≥ 50%1-49%≤ 1%RegimenMono-nivoCombinationCombinationCombinationNo surg12116PDirAEirAE 1 Declined 1PDDelayed surg < 2w3011Median week from last NA to surg4555R01110141146Minimally invasive (MI)11 (23.9)9 (19.6)13 (28.3)11 (23.9)44 (95.7)MI to thoracotomy01102 (4.3)Lobectomy10 (21.7)6 (13.0)12 (26.1)11 (23.9)37 (80.4)Pneumonectomy01102 (4.3)Other13105Lymph node Downstaging4 (8.7)7 (15.2)7 (15.2)8 (17.4)26 (56.5)pCR (%)18.250.021.427.3MPR (%)18.280.064.354.5Pre-NA (+)5 (14.7)9 (26.5)11 (32.3)9 (26.5)34ctDNA clearance (%)14.377.869.266.7Post-surg (-)4 (14.3)8 (28.6)11 (39.3)5 (17.8)28 Open table in a new tab ConclusionsWe prefer chemoimmunotherapy as neoadjuvant treatment regardless of PD-L1 expression. ctDNA clearance would be a predictor of favorable pathological and survival outcomes.Clinical trial identificationNCT04015778.Legal entity responsible for the studyChinese Thoracic Oncology Group, CTONG.FundingBristol Myers Squibb.DisclosureW. Zhong: Non-Financial Interests, Personal, Board Member in the Educational Committee (mainly participated in educational event organization): International Association for the Study of Lung Cancer (IASLC). Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi, Yunhan; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). All other authors have declared no conflicts of interest. BackgroundWe profiled clinical and biomarker data from this prospective, multicenter, phase II study evaluating the efficacy and safety of NA nivo with or without platinum-doublet chemotherapy based on PD-L1 status (NCT04015778). We profiled clinical and biomarker data from this prospective, multicenter, phase II study evaluating the efficacy and safety of NA nivo with or without platinum-doublet chemotherapy based on PD-L1 status (NCT04015778). MethodsPatients (pts) had resectable clinical stage IIA-IIIB (AJCC 8th) NSCLC and ECOG PS 0/1 with no EGFR/ALK variations. Pts received mono-nivo 360mg treatment (tx) for ≤3 cycles q3w or nivo 360mg + nab-paclitaxel 185mg/m2 (d1, d8) + carboplatin AUC5 for ≤3 cycles q3w based on PD-L1 status. Primary endpoint was major pathological response (MPR: ≤10% viable tumor cells). Key secondary endpoints included pathologic complete response (pCR), objective response rate (ORR, RECIST v1.1), adverse events (AEs) including treatment-related (TRAE) and immune-related (irAE). We correlated PD-L1 status and perioperative ctDNA presence with pCR and event-free survival (EFS). Patients (pts) had resectable clinical stage IIA-IIIB (AJCC 8th) NSCLC and ECOG PS 0/1 with no EGFR/ALK variations. Pts received mono-nivo 360mg treatment (tx) for ≤3 cycles q3w or nivo 360mg + nab-paclitaxel 185mg/m2 (d1, d8) + carboplatin AUC5 for ≤3 cycles q3w based on PD-L1 status. Primary endpoint was major pathological response (MPR: ≤10% viable tumor cells). Key secondary endpoints included pathologic complete response (pCR), objective response rate (ORR, RECIST v1.1), adverse events (AEs) including treatment-related (TRAE) and immune-related (irAE). We correlated PD-L1 status and perioperative ctDNA presence with pCR and event-free survival (EFS). ResultsTable: LBA2ParameterA1A2B1B2SumEnrolled1212161252PD-L1≥ 50%≥ 50%1-49%≤ 1%RegimenMono-nivoCombinationCombinationCombinationNo surg12116PDirAEirAE 1 Declined 1PDDelayed surg < 2w3011Median week from last NA to surg4555R01110141146Minimally invasive (MI)11 (23.9)9 (19.6)13 (28.3)11 (23.9)44 (95.7)MI to thoracotomy01102 (4.3)Lobectomy10 (21.7)6 (13.0)12 (26.1)11 (23.9)37 (80.4)Pneumonectomy01102 (4.3)Other13105Lymph node Downstaging4 (8.7)7 (15.2)7 (15.2)8 (17.4)26 (56.5)pCR (%)18.250.021.427.3MPR (%)18.280.064.354.5Pre-NA (+)5 (14.7)9 (26.5)11 (32.3)9 (26.5)34ctDNA clearance (%)14.377.869.266.7Post-surg (-)4 (14.3)8 (28.6)11 (39.3)5 (17.8)28 Open table in a new tab ConclusionsWe prefer chemoimmunotherapy as neoadjuvant treatment regardless of PD-L1 expression. ctDNA clearance would be a predictor of favorable pathological and survival outcomes. We prefer chemoimmunotherapy as neoadjuvant treatment regardless of PD-L1 expression. ctDNA clearance would be a predictor of favorable pathological and survival outcomes.