LBA2 - Phase II study of PD-L1 Expression Guidance on Neoadjuvant (NA) Nivolumab (Nivo) Monotherapy with or without platinum-doublet Chemotherapy in Resectable NSCLC

Background

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).

Methods

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).

Results

From 08/08/2019 to 08/16/2021 52 pts were accrued and 46 had surgery (surg outcome in the table). The pre-surg ORR was 51.9% (27/52) with 2 CR. 25/46 (54.3%) achieved MPR of which 13 (28.3%) were pCR. In PD-L1 ≥ 50% group mono-nivo achieved 18.2% MPR while chemoimmunotherapy achieved 80%. AEs occurred in all pts during NA tx, including irAEs in 36/52 (69.2%) and 3 pts discontinued NA tx. 45 (97.8%) pts had sufficient tissue for tumor-informed MRD. MRD was detected in 84.4% in pre-NA (n=38), 91.1% in post-NA (n=41) and 80.0% in post-surg samples (n=36). Significant ctDNA clearance post-NA was seen in pts with pCR vs non- pCR (OR=8.56, 95% CI: 1.22-Inf, p=0.03). With a median follow-up of 25.1 months (95% CI: 22.4-27.7m), 2yr-EFS rate for pts with MRD– (both post-NA and -surg) vs. MRD+ (either post-NA or -surg) was 86.6% vs 47.3% (HR, 0.20; 95% CI: 0.04, 0.94; p=0.02). Table: LBA2

Conclusions

We prefer chemoimmunotherapy as neoadjuvant treatment regardless of PD-L1 expression. ctDNA clearance would be a predictor of favorable pathological and survival outcomes.

Clinical trial identification

NCT04015778.

Legal entity responsible for the study

Chinese Thoracic Oncology Group, CTONG.

Funding

Bristol Myers Squibb.

Disclosure

W. 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.