145MO - Updated survival, efficacy and safety of adjuvant (adj) atezolizumab (atezo) after neoadjuvant (neoadj) atezo in the phase II LCMC3 study

Background

Neoadj chemoimmunotherapy (IO) treatment (tx) without adj tx has shown impressive DFS outcomes but the role of adj IO after neoadj IO is unclear. LCMC3, an open-label, single-arm ph II study of neoadj atezo (anti–PD-L1) with optional adj atezo in patients (pts) with early-stage non-small cell lung cancer (NSCLC). Here we report updated DFS, OS and safety in pts who received adj atezo vs pts who did not.

Methods

Eligible pts aged ≥18 y had resectable stage IB-IIIA or select IIIB NSCLC and ECOG PS 0-1. Pts received neoadj atezo 1200 mg IV for ≤2 cycles (Days 1 and 22) followed by surgery (Day 40 ± 10). Pts without progression were offered the option to receive adj atezo every 3 weeks for ≤12 months. The primary endpoint was MPR rate (≤10% viable tumor cells at surgery) in pts without EGFR/ALK mutations. Exploratory endpoints included DFS and OS. Safety was assessed during the adj phase.

Results

Data cutoff was Oct 21, 2022. The primary efficacy population (PEP) was 137 pts without EGFR/ALK alterations who had surgery and MPR assessment. The updated 3-y DFS and OS rate for the entire group was 72% and 82%, for stage I/II was 75% and 82%, and for stage III was 68% and 81%, respectively. In the PEP, 53 pts (39%) received adj atezo and 84 (61%) did not. While not randomized, these groups were clinically well balanced. The 3-y DFS rate was 83% with adj atezo vs 64% without adj atezo (HR, 0.43; 95% CI: 0.21, 0.90; P = 0.025). In pts without MPR (n = 108) 3-y DFS for adj atezo vs without adj atezo was 80% vs 62% (HR, 0.48; 95% CI: 0.20, 1.12; P = 0.088) and 3-y OS was 87% vs 75% (HR, 0.49; 95% CI: 0.17, 1.46; P = 0.202). In the adj atezo safety population (n = 57), there were 11 treatment-related adverse events (19%; Gr 3/4, 16%) leading to discontinuation of adj atezo.

Conclusions

This exploratory analysis revealed that LCMC3 pts with resectable NSCLC who received adj atezo had improved DFS and showed a trend toward improved OS vs pts who did not receive adj atezo. Furthermore, the non-MPR subgroup had the same trend toward improved DFS and OS with adj atezo vs pts who did not receive adj atezo. Adj atezo was well tolerated, with no new safety concerns. These data suggest that adding adj IO to neoadj IO may result in improved outcomes.

Clinical trial identification

NCT02927301.

Editorial acknowledgement

Editorial assistance was provided by Michael Williams PhD of Health Interactions Inc and funded by Genentech Inc.

Legal entity responsible for the study

Genentech Inc.

Funding

Genentech Inc.

Disclosure

D.P. Carbone: Financial Interests, Personal, Other, Consultant/Independent Contractor: Iovance Biotherapies; Financial Interests, Personal, Advisory Role: Janssen, Jazz, Sanofi Genzyme, Regeneron, Glaxo-Smith Kline, Iovance Biotherapies, AbbVie; Financial Interests, Personal, Other, DMC: Lilly; Financial Interests, Personal, Other, Lung Cancer Symposium: Roche Taiwan; Financial Interests, Personal, Other, Moderator, Lung Cancer Screening Program: AstraZeneca; Financial Interests, Personal, Other, Education Program: Onc Live; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Other, Honorarium Recipient: AstraZeneca. S.N. Waqar: Financial Interests, Institutional, Invited Speaker, Institutional PI for Research study: Spectrum Pharmaceuticals, Lilly, Pfizer, Genentech/Roche, Daiichi Sankyo, Newlink Genetics, EMD Serono, Puma Biotechnology, Novartis, Xcovery, Synermore biologics, Celgene, Vertex, Bristol-Myers Squibb, Stem CentRx, Hengrui Therapeutics, Checkpoint Therapeutics, Ignyta, AstraZeneca, ARIAD, Roche, Merck; Financial Interests, Institutional, Other, This funding provides effort for Dr. Waqar to support and oversee the Lung-MAP master protocol and sub study activities: SWOG-Clinical Trials Partnership; Financial Interests, Personal and Institutional, Other, Chair of Data Safety Monitoring Board for Study: Hoosier Cancer Research Network. J. Chaft: Financial Interests, Personal, Other, Consultant: AstraZeneca, Flame Biosciences, Genentech, BMS, Merck, Guardant Health, Janssen, Novartis, Regeneron, Arcus Biosciences. M.G. Kris: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BerGenBio, Pfizer, Janssen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Other, Editorial support: Genentech. B.E. Johnson: Financial Interests, Personal, Full or part-time Employment, Post Marketing Royalties for EGFR mutation testing: Dana-Farber Cancer Institute; Financial Interests, Personal, Other, Independent Contractor: Novartis, Checkpoint Therapeutics, Hummingbird Diagnostics, Daiichi Sankyo, AstraZeneca, G1 Therapeutics, BlueDotBio, GSK, Hengrui Therapeutics, Simcere Pharmaceutical; Financial Interests, Personal, Other, Steering Committee member: Pfizer. J.M. Lee: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Astrazeneca, Roche/Genentech, Novartis; Financial Interests, Personal, Invited Speaker, LCMC3, LCMC4, NAUTIKA-1: Roche/Genentech; Financial Interests, Personal, Invited Speaker, CANOPY-N, GEOMETRY-1: Novartis. I.I. Wistuba: Financial Interests, Personal, Advisory Board: Genentech/Roche, Bristol-Myers Squibb, AstraZeneca, Merck, GlaxoSimthKline, Oncocyte, Flame, Daiichi Sankyo, Amgen, Novartis, Sanofi, Jansen, Regeneron, Merus; Financial Interests, Personal, Invited Speaker: Guardant Health, MSD, Roche, Pfizer, Merck; Financial Interests, Institutional, Funding: Genentech, Medimmune/AstraZeneca, Merck, Adaptimmune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis, Akoya. D. Kwiatkowski: Financial Interests, Personal, Other, consultant: Guidepoint, Bridgebio, AADI; Financial Interests, Institutional, Research Grant, research grant: Genentech, AADI, Revolution Medicines. P.A. Bunn: Financial Interests, Personal, Advisory Board: Verastem, Ascentage, CStone; Financial Interests, Personal, Other, DMC Member: Merck, BMS; Financial Interests, Personal, Other, Independent Contractor: Lilly. K. Schulze: Financial Interests, Personal, Full or part-time Employment: Genentech Inc.; Financial Interests, Personal, Stocks/Shares: Roche. A.M. Johnson: Financial Interests, Institutional, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech; Financial Interests, Personal and Institutional, Other, Employee of Genentech Roche – research funding for clinical trials: Genentech; Other, Personal, Other, Employee of Genentech Roche: Genentech. E. Brandao: Financial Interests, Personal, Full or part-time Employment: Genentech Inc.; Financial Interests, Personal, Stocks/Shares: Roche. M. Awad: Financial Interests, Personal, Research Grant: BMS, Lilly, Genentech, AstraZeneca, Amgen; Financial Interests, Personal, Other, Consultant: BMS, Merck, Genentech, AstraZeneca, Mirati, Blueprint Medicine, AbbVie, Gritstone, NextCure, EMD Serono. K. Reckamp: Financial Interests, Personal, Other, consultant: Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GlaxoSmithKline, Janssen, Lilly, Mirati, Takeda; Financial Interests, Personal, Advisory Board: EMD Soreno, Merck KGA; Financial Interests, Personal, Invited Speaker: Seattle Genetics,; Financial Interests, Institutional, Invited Speaker: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen. A.C. Chiang: Financial Interests, Personal, Advisory Board, and consulting: AstraZeneca; Financial Interests, Personal, Advisory Board: Daichi, Genentech; Financial Interests, Institutional, Officer, SWOG Executive Officer for Lung and Breast: SWOG; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, Genentech, BMS. A. Nicholas: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. V. Rusch: Financial Interests, Personal, Research Grant, Institutional clinical trial (Surgical PI): Genentech.