Abstract 920P
Background
Avelumab (anti–PD-L1) has shown antitumor activity in patients with various solid tumors. We report results from a cohort of patients with R/M SCCHN treated with avelumab monotherapy in the JAVELIN Solid Tumor phase I trial (NCT01772004).
Methods
Eligible patients had platinum-refractory/ineligible R/M SCCHN and received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Assessments included objective response rate (ORR) and progression-free survival (PFS) by investigator and independent review committee (IRC), overall survival (OS), and safety. PD-L1+ status (expression in ≥1% of tumor cells [73-10 assay]) and HPV status (p16 immunohistochemistry) were assessed centrally.
Results
153 patients were enrolled and received avelumab; 117 (76.5%) and 29 (19.0%) had ≥2 and ≥4 prior lines of therapy, respectively (median, 2 [range, 1-7]). At data cut-off (31 Dec 2017), median follow-up was 27.9 mo (range, 25-32 mo), and 10 patients (6.5%) remained on treatment. Based on IRC and investigator assessment, respectively, the ORR was 9.2% (95% CI: 5.1%-14.9%) and 13.1% (95% CI: 8.2%-19.5%); median PFS (95% CI) was 1.4 mo (1.4-2.6 mo) and 1.8 mo (1.4-2.7 mo). Median OS was 8.0 mo (95% CI: 6.5-10.2 mo), and 1- and 2-year OS rates were 35.9% (95% CI: 28.3%-43.6%) and 17.1% (95% CI: 11.5%-23.7%), respectively. In patients with PD-L1+ (n=107) or PD-L1− (n=30) tumors, ORR (95% CI) by IRC was 10.3% (5.2%-17.7%) vs 3.3% (0.1%-17.2%) and by investigator was 15.0% (8.8%-23.1%) vs 6.7% (0.8%-22.1%), respectively. In HPV+ (n=39) and HPV− (n=99) subgroups, ORR (95% CI) by IRC was 15.4% (5.9%-30.5%) vs 5.1% (1.7%-11.4%) and by investigator was 17.9% (7.5%-33.5%) vs 11.1% (5.7%-19.0%), respectively. Any-grade treatment-related adverse events (TRAEs) occurred in 83 patients (54.2%), including grade ≥3 TRAEs in 10 (6.5%), and led to discontinuation in 4 (2.6%). Serious TRAEs occurred in 6 patients (3.9%). No treatment-related deaths occurred.
Conclusions
Avelumab showed clinical activity and an acceptable safety profile in heavily pretreated patients with platinum-refractory/ineligible R/M SCCHN.
Clinical trial identification
NCT01772004.
Editorial acknowledgement
Medical writing assistance was provided by Eleanor Green of ClinicalThinking and funded by Merck KGaA, Darmstadt, Germany and Pfizer.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany and Pfizer.
Funding
Merck KGaA, Darmstadt, Germany and Pfizer.
Disclosure
J. Guigay: Advisory/Consultancy, Research grant/Funding (institution): EMD Serono; a business of Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Merck & Co. K-W. Lee: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Genexine; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Research grant/Funding (institution): AstraZeneca/MedImmune; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): MacroGenics; Research grant/Funding (institution): Green Cross Corporation; Research grant/Funding (institution): Five Prime Therapeutics; Research grant/Funding (institution): Pharmacyclics LLC, an AbbVie Company; Research grant/Funding (institution): LSK BioPharma; Research grant/Funding (institution): ALX Oncology; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): ASLAN; Research grant/Funding (institution): Array BioPharma. M.R. Patel: Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Pharmacyclics; Honoraria (self): Bayer; Honoraria (self): Janssen; Honoraria (self): Genentech; Honoraria (self): AbbVie; Speaker Bureau/Expert testimony, Research grant/Funding (institution): EMD Serono; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Speaker Bureau/Expert testimony: Exelixis; Research grant/Funding (institution): Acerta Pharma; Research grant/Funding (institution): ADC Therapeutics; Research grant/Funding (institution): Agenus; Research grant/Funding (institution): Aileron Therapeutics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bicycle Therapeutics; Research grant/Funding (institution): BioNTech; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Calithera; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Checkpoint Therapeutics; Research grant/Funding (institution): Ciclomed; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Cyteir Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Effector Therapeutics; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Evelo Biosciences; Research grant/Funding (institution): Forma Therapeutics; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Hengrui; Research grant/Funding (institution): Hutchinson MediPharma; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Jacobio; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Jounce Therapeutics; Research grant/Funding (institution): Klus Pharma; Research grant/Funding (institution): Kymab; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): LSK Biopartners; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): Millennium Pharmaceuticals; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): ModernaTX; Research grant/Funding (institution): Phoenix Molecular Designs; Research grant/Funding (institution): Placon Therapeutics; Research grant/Funding (institution): Portola Pharmaceuticals; Research grant/Funding (institution): Prelude Therapeutics; Research grant/Funding (institution): Qilu Puget Sound Biotherapeutics; Research grant/Funding (institution): Revolution Medicines; Research grant/Funding (institution): Ribon Therapeutics; Research grant/Funding (institution): Seven and Eight Biopharmaceuticals; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Synthorx; Research grant/Funding (institution): Stemline Therapeutics; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): TopAlliance; Research grant/Funding (institution): Vedanta; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Vigeo; Research grant/Funding (institution): Xencor. A. Daste: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck KGaA. D.J. Wong: Advisory/Consultancy, Research grant/Funding (self): Sanofi-Aventis; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Merck KGaA; Research grant/Funding (self): Kura; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Regeneron; Research grant/Funding (self): Genentech; Research grant/Funding (self): Fstar; Research grant/Funding (self): Astellas; Research grant/Funding (self): Enzychem; Research grant/Funding (self): Iovance; Research grant/Funding (self): Pfizer. M. Gordon: Advisory/Consultancy: Tracon Pharma; Advisory/Consultancy: Redhill; Advisory/Consultancy: Deciphera; Advisory/Consultancy: ImaginAb; Shareholder/Stockholder/Stock options: Medelis; Shareholder/Stockholder/Stock options: Caremission. M. Gutierrez: Advisory/Consultancy: Guardant 360; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): Array; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Care Progress; Research grant/Funding (institution): Compass; Research grant/Funding (institution): Constellation; Research grant/Funding (institution): Cyteir; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Esanex; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Infinity; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Medlmmune; Research grant/Funding (institution): Mirati; Research grant/Funding (institution): Moderna; Research grant/Funding (institution): Nextcure Pharma; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Checkpoint; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Silenseed; Research grant/Funding (institution): Vendanta; Shareholder/Stockholder/Stock options: Cota Healthcare; Full/Part-time employment: Regional Cancer Care Associates. A. Balmanoukian: Speaker Bureau/Expert testimony, Self and Immediate Family Member: Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Self and Immediate Family Member: Genentech; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Self and Immediate Family Member: Merck KGaA; Speaker Bureau/Expert testimony, Self and Immediate Family Member: AstraZeneca; Speaker Bureau/Expert testimony, Self and Immediate Family Member: Eli Lilly; Research grant/Funding (institution): Arcus; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Medlmmune. C. Le Tourneau: Honoraria (self), Travel/Accommodation/Expenses: Merck & Co.; Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: EMD Serono; Honoraria (self): Seattle Genetics; Honoraria (self): GlaxoSmithKline; Honoraria (self): Roche; Honoraria (self): Amgen; Honoraria (self): Rakuten; Honoraria (self): Nanobiotix; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca. D. Vansteene: Advisory/Consultancy: Nutricia; Advisory/Consultancy: Nestle. U. Keilholz: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck & Co.; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck KGaA; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer.P. Schöffski: Honoraria (self): Deciphera; Honoraria (self), Advisory/Consultancy: Blueprint Medicines; Honoraria (self): Boehringer Ingelheim; Advisory/Consultancy: Lilly; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Plexxikon; Advisory/Consultancy: Loxo; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Deciphera; Advisory/Consultancy: Genmab; Advisory/Consultancy: Servier; Advisory/Consultancy: Intellisphere; Advisory/Consultancy: Transgene; Advisory/Consultancy: Merck; Advisory/Consultancy: Adaptimmune; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): CoBioRes NV; Research grant/Funding (institution): PharmaMar; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Ipsen. H.J. Grote: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. D. Zhou: Full/Part-time employment: Merck Serono Pharmaceutical R&D Co., Beijing, China; an affiliate of Merck KGaA, Darmstadt, Germany. M. Bajars: Full/Part-time employment: EMD Serono Research & Development Institute, Inc.; a business of Merck KGaA, Darmstadt, Germany. All other authors have declared no conflicts of interest.