1493PLong-term avelumab treatment in patients with advanced non-small cell lung cancer (NSCLC): Post hoc analyses from JAVELIN solid tumour

Abstract Background Avelumab, a human IgG1 anti–PD-L1 monoclonal antibody, is an approved treatment for metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma. We performed descriptive post hoc analyses to explore characteristics of patients with NSCLC from the JAVELIN Solid Tumor phase I trial (NCT01772004) who received long-term avelumab treatment (>2-yrs) as a surrogate for long-term clinical benefit. Methods Patients with NSCLC were pooled from 2 dose-expansion cohorts enrolled with no prior treatment for metastatic/recurrent disease (first-line [1L]) or with disease progression after prior platinum doublet therapy (second-line [2L]). PD-L1 expression in tumor cells was assessed using the Dako 73-10 assay. Results As of 24 Oct 2018, duration of avelumab treatment was >2-yrs in 35 of 340 patients (10.3%) and ≤2-yrs in 305 of 340 (89.7%). At baseline (data cutoff: 15 Feb 2017), patients who subsequently received >2-yr vs≤2-yr treatment had a higher proportion with prior radiotherapy (51.4% vs 37.0%), better performance status (ECOG PS 0 in 37.1% vs 28.9%), a lower proportion with liver (11.4% vs 19.0%) or bone (14.3% vs 22.3%) metastases, and a smaller tumor burden (median, 52 vs 70mm). A higher proportion of patients with >2-yr vs≤2-yr treatment had clinical benefit (response or stable disease) on prior chemotherapy (40.0% vs 25.9%, respectively; not applicable in 31.4% vs 39.7%; not evaluable in 17.1% vs 8.2%). The proportion with PD-L1+ tumors was comparable in those with >2-yr or≤2-yr treatment using PD-L1 cutoffs of≥1% (68.6% vs 61.0%) and ≥80% (25.7% vs 23.0%), although a high proportion were nonevaluable for PD-L1 expression (25.6%). Of patients with >2-yr treatment, 18 continued treatment after RECIST-defined progression and had a decrease in tumor burden or maintained clinical benefit. Conclusions Retrospective post hoc analyses suggest that patients with NSCLC who had long-term benefit with 1L or 2L avelumab had better performance status, less aggressive disease, prior radiotherapy, and previous benefit on chemotherapy at baseline. Clinical trial identification NCT01772004. Editorial acknowledgement ClinicalThinking; funded by Merck Healthcare KGaA and Pfizer Inc. Legal entity responsible for the study Merck Healthcare KGaA. Funding Merck Healthcare KGaA and Pfizer Inc. Disclosure B. Hrinczenko: Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Merrimack Pharma; Research grant / Funding (institution): Endocyte; Research grant / Funding (institution): Amgen. D. Spigel: Leadership role: Cetennial Medical Center; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck & Co.; Advisory / Consultancy: Moderna Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Nektar; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: TRM Oncology; Advisory / Consultancy: Precision Oncology; Advisory / Consultancy: Evelo Therapeutics; Advisory / Consultancy: Illumina; Advisory / Consultancy: PharmaMar; Research grant / Funding (institution): University of Texas Southwestern Medical Center - Simmons Cancer Center; Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): Neon Therapeutics; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): GRAIL; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Aeglea Biotherapeutics; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): ARMO BioSciences; Research grant / Funding (institution): Millennium; Travel / Accommodation / Expenses: Genzyme; Travel / Accommodation / Expenses: Intuitive Surgical; Travel / Accommodation / Expenses: Purdue Pharma; Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Research grant / Funding (institution): Sysmex. M.H. Taylor: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Blueprint; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Loxo; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Array ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ArQule, Inc. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Merck KGaA. S. Goel: Research grant / Funding (institution): EMD Serono. J. Leach: Full / Part-time employment, Employed as of Sep 2016 to Sep 2017: PRA Health Sciences ; Research grant / Funding (institution): Dynarax ; Research grant / Funding (institution): Geistlich . D.J. Wong: Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck & Co.; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): KURA Oncology; Research grant / Funding (institution): Roche-Genentech; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): FSTAR; Research grant / Funding (institution): Astellas. K. Kelly: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck & Co.; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): EMD Serono; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Regeneron; Research grant / Funding (self): Five Prime; Travel / Accommodation / Expenses: Lilly; Licensing / Royalties: UpToDate. M. Bajars: Full / Part-time employment: EMD Serono. J. Manitz: Full / Part-time employment: EMD Serono. M. Ruisi: Full / Part-time employment: EMD Serono. J.L. Gulley: Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Astellas Medivation; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): NantBioScience; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck & Co. All other authors have declared no conflicts of interest.