1215O - Neoadjuvant atezolizumab (A) for resectable non-small cell lung cancer (NSCLC): results from the phase II PRINCEPS trial.

Background

Neoadjuvant immune checkpoint inhibitors induce major pathologic response (MPR) rates in 17- 45% of NSCLCs. We report the results of a phase 2 trial of neoadjuvant A for NSCLC.

Methods

Patient (pts) with clinical stage IA (≥ 2 cm)-IIIA non N2 NSCLC eligible for surgery, PS 0-1, received 1 injection of A (1200 mg IV D1) followed by surgery between D21-D28. The primary endpoint was the rate of pts without major toxicities or morbidities from D1 until 1 month after the surgery. Fresh tumour tissue was analysed within 4 hours after surgery. Response by RECIST1.1 and major pathological response (MPR; ≤10% viable tumour) were assessed.

Results

From December 2016 to February 2020, 30 pts were enrolled in two centres. The mean age of pts was 64, 50% were female, 7% never smokers, 83% had adenocarcinomas. Pathological stages were I (n=15, 50%), II (n=6, 20%) III (n=9, 30%). All pts had their planned surgery, none were delayed by >15 days. 29 had R0 resection, 1 had R1. Three pts experienced surgical complications: 1 respiratory distress grade 3 with sepsis grade 4, 1 heart block atrioventricular and 1 paresthesia grade 1. There was no grade 5 toxicity. Treatment-related adverse effects (TRAEs) included only one grade 1 parietal pain related to surgery. No RECIST radiological response and no MPR were observed. After A, 15/29 tumours were PD-L1 TC3 or IC3 based on the SP142 assay. 17/30 (56%) tumours had necrosis (med. 5% of tumour surface, 0-80). 20/29 cases had histopathological features of response according to the immune-related pathologic response criteria (irPRC), with isolated or combined features of immune activation (19/20), tissue repair (15/20) and/or tumour cell death (9/20).NGS (11 genes) was performed in 23 tumours resulting in 14 TP53 mutations (mut), 7 KRAS mutations , 3 EGFR mutations, 1 wild-type, 1 STK11 mutations (in a tumour with 80% necrosis).

Conclusions

Surgery after one infusion of A was safe. The short delay between A and surgery might explain the absence of MPR.

Clinical trial identification

NCT02994576.

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy.

Funding

Roche-Genentech.

Disclosure

B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Inivata; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; Research grant/Funding (institution): OSE immunotherapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharma Mar; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tiziana Pharma; Research grant/Funding (institution): Tolero Pharmace. J. Adam: Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): msd; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self): BMS. N. Chaput-Gras: Research grant/Funding (institution): Roche. D. Planchard: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Merck KGaA; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche-Genentech; Advisory/Consultancy: Samsung; Honoraria (self), Advisory/Consultancy: Per CME; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Prime oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novaris. L. Mezquita: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self): Tecnofarma; Honoraria (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Research grant/Funding (self): Boehringer Ingelheim. J. Remon Masip: Travel/Accommodation/Expenses: Ose Pharma; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Pfizer; Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: BMS. P. Lavaud: Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Janssen; Travel/Accommodation/Expenses: Mundi Pharma; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: AstraZeneca. C. Naltet: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: pfizer. A. Gazzah: Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): bms; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Johnson & Johnson; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): NH TherAGuiX. B. Duchemann: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): MSD; Travel/Accommodation/Expenses: Oxyvie; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: AstraZeneca. F. Barlesi: Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): ACEA; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Ipsen; Research grant/Funding (self): Ignyta; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Innate Pharma; Research grant/Funding (institution): Loxo; Research grant/Funding (institution): MedImmune; Honoraria (self), Research grant/Funding (institution): Merck KGaA; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Research grant/Funding (self): Takeda; Honoraria (self), Research grant/Funding (institution): Pierre Fabre. J-C. Soria: Honoraria (self): Clovis; Honoraria (self), Full/Part-time employment: AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Grammamabs; Honoraria (self): Mission Therapeutics; Honoraria (self): Merus; Honoraria (self): Eli Lilly; Shareholder/Stockholder/Stock options: Gritstone; Honoraria (self): Symphogen; Honoraria (self): Tarveda; Honoraria (self): Pfizer; Honoraria (self): Pharma Mar; Honoraria (self): Roche-Genentech; Honoraria (self): Sanofi; Honoraria (self): Servier; Honoraria (self): Bayer; Honoraria (self): Blend therapeutics; Honoraria (self): Astex; Honoraria (self): Pierre Fabre. C. Caramella: Honoraria (self): pfizer; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Roche. All other authors have declared no conflicts of interest.