LBA37 - A randomized, multicentric phase II study of preoperative nivolumab plus relatlimab or nivolumab in patients with resectable non-small cell lung cancer (NEOpredict-Lung)

Background

Preoperative immune checkpoint inhibitor therapy (PICIT) is a promising approach in curative treatment of non-small-cell lung cancer (NSCLC). This study explores the feasibility and efficacy of targeting PD-1 and LAG-3 prior to resection.

Methods

Patients with histologically confirmed NSCLC stage IB, II or IIIA (UICC 8^th edition) were randomized to receive two preoperative doses (q14d) of nivolumab (240 mg, arm A), or nivolumab (240 mg) plus relatlimab (80 mg, arm B). The primary study endpoint was the feasibility of curatively intended surgery within 43 days of start of PICIT. Secondary endpoints include pathological and radiological response rates, disease-free and overall survival rates (DFS, OS) and safety. Exploratory endpoints are addressed by translational research.

Results

From March 4, 2020 to July 15, 2022, 60 patients have been randomized. The primary endpoint was met by all patients. R0 resection rate was 98%, excluding 2 patients with pleural carcinosis, which had been undetected by preoperative imaging. PICIT-related adverse events were as expected with grade ≥ 3 events in 4 (arm A) and 2 (arm B) patients. Two patients treated in arm A died within 90 days of surgery. The 12 months OS rate across both arms was 96% (95% CI: 83-99%), the DFS rate was 91% (78-97%). Radiological response rates were 11% (arm A) and 27% (arm B) per RECIST (full population), and 41% (arm A) and 38% (B) per PERCIST (30 patients from one center). Complete or major histopathological response rates were 28% (arm A) and 32% (arm B). In 60% (arm A) and 71% (arm B) of resections after PICIT ≤ 50% vital tumor cells were observed. Table: 000LBA37

Conclusions

Preoperative immune checkpoint inhibition with nivolumab and relatlimab is safe and feasible in patients with curatively resectable NSCLC. High histopathological response rates indicate clinical efficacy, which merits further study supplementing with biomarker analyses for future patient selection.

Clinical trial identification

NCT04205552.

Editorial acknowledgement

Legal entity responsible for the study

University Hospital Essen.

Funding

Bristol Myers Squibb.

Disclosure

M.H.H. Schuler: Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Roche; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, AstraZeneca; Non-Financial Interests, Principal Investigator, Member, Study Steering Board: Janssen. K. Cuppens: Financial Interests, Personal, Advisory Board: Hoffmann-La Roche, AstraZeneca, Merck Sharp Dohme, Bristol-Myers-Squibb, Boehringer-Ingelheim, Bayer; Financial Interests, Personal, Invited Speaker: Pfizer, Bristol-Myers-Squibb, Merck Sharp Dohme, Hoffmann-La Roche; Financial Interests, Personal, Expert Testimony: Merck Sharp Dohme, AstraZeneca. T. Ploenes: Financial Interests, Personal, Invited Speaker: Roche, BMS; Financial Interests, Personal, Advisory Board: BMS, Novocure. M. Wiesweg: Financial Interests, Personal, Invited Speaker: Amgen, Roche, Takeda; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Pfizer, Roche; Financial Interests, Personal, Expert Testimony: GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Funding: Bristol-Myers Squibb. K. Darwiche: Financial Interests, Institutional, Invited Speaker: Olympus, Boston Scientific, Broncus Medical, Erbe, Böhringer Ingelheim, Storz, AstraZeneca; Financial Interests, Personal, Advisory Role: bess, Boston Scientific, Broncus Medical, Fujifilm, FreeFlow, Olympus, Storz, PulmonX, Böhringer Ingelheim, Morair Medtech, Medtronic; Financial Interests, Institutional, Research Grant: Pulmonx, PneumRx, Nuveira, Epigenomics, Broncus, Novartis, Roche, Ambu, Gala Therapeutics. A. Schramm: Financial Interests, Institutional, Funding, Funding of translational research projects outside and within clinical studies.: Bristol Myers Squibb. B. Maes: Financial Interests, Personal, Advisory Board: Servier, AstraZeneca, Illumina; Financial Interests, Personal, Invited Speaker: Pfizer, Illumina; Financial Interests, Institutional, Invited Speaker: Illumina, SeqOne; Non-Financial Interests, Principal Investigator: BSMO. H. Schildhaus: Financial Interests, Personal, Advisory Board: MSD, BMS, Roche Pharma, Novartis Oncology, AstraZeneca, Eisai, Takeda, ZytoVision, Zytomed Systems, Molecular Health; Financial Interests, Institutional, Research Grant: Novartis Oncology; Financial Interests, Personal, Full or part-time Employment: Targos Molecular Pathology Inc.. H. Hautzel: Financial Interests, Personal, Other, Travel Fees: PARI Gmbh; Financial Interests, Institutional, Research Grant: PARI Gmbh. P. Baas: Financial Interests, Institutional, Advisory Board: BMS, MSD, Beigene; Financial Interests, Institutional, Research Grant: MSD, BMS. C. Aigner: Financial Interests, Personal, Advisory Board: BMS, Roche, AstraZeneca, Biotest; Financial Interests, Personal, Invited Speaker: MSD, Roche, AstraZeneca; Financial Interests, Institutional, Invited Speaker: BMS, PharmaCept. All other authors have declared no conflicts of interest.