In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab (anti–PD-L1 IgG1 antibody) 1L maintenance + BSC significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC without disease progression with 1L induction chemotherapy in all randomized pts and pts with PD-L1+ tumors. We report exploratory biomarker analyses.
Tumor biopsies were collected prior to randomization. Tumor analyses included PD-L1 (Ventana SP263 assay) and CD8 immunohistochemistry, whole-exome sequencing (including
Increased OS benefit with avelumab 1L maintenance + BSC vs BSC alone was positively associated with CD8+ T cells in the invasive margin or tumor center, high tumor mutation burden, and tumor gene expression signatures of innate and adaptive immune response. Increased OS benefit was also positively associated with the number of
OS benefits of avelumab 1L maintenance in pts with advanced UC are positively associated with biomarkers of immune activity and negatively associated with biomarkers of tumor homeostasis and chronic inflammation.
NCT02603432.
Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking (Hamilton, NJ, USA) and funded by Pfizer and Merck KGaA, Darmstadt, Germany.
Pfizer.
This study was sponsored by Pfizer, and is part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany.
T.B. Powles: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genetech/Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Research to Practice; Honoraria (self), Travel/Accommodation/Expenses: Ferring; Honoraria (self): Gerson Lehrman Group; Honoraria (self): Janssen Research & Development. Y. Loriot: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Honoraria (self): Sanofi; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics. J. Bellmunt: Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genetech; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck. C.N. Sternberg: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday; Advisory/Consultancy: Astellas Pharma; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genzyme; Research grant/Funding (institution): Aragon Pharmaceuticals; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelhein; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Myovant Sciences; Research grant/Funding (institution): Nektar. S. Sridhar: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Astellas. D.P. Petrylak: Advisory/Consultancy, Research grant/Funding (institution): Ada Cap (Advanced Accelerator Applications); Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Bicycle Therapeutics; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Exelixis; Research grant/Funding (institution): Endocyte; Advisory/Consultancy: Incyte; Advisory/Consultancy: Janssen; Research grant/Funding (institution): Genetech; Research grant/Funding (institution): Innocrin; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Pharmacyclics; Research grant/Funding (institution): Progenies; Advisory/Consultancy, Research grant/Funding (institution): Roche Laboratories; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Sanofi Aventis; Advisory/Consultancy: Urogen; Shareholder/Stockholder/Stock options, Ownership Interest/Investment: Bellicum; Shareholder/Stockholder/Stock options, Ownership Interest/Investment (Sold 10/2019): Tyme. L.M. Dourthe: Honoraria (self), Advisory/Consultancy: Astellas ; Honoraria (self), Advisory/Consultancy: Bayer; Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. C. Alvarez-Fernandez: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Boehringer Ingelheim; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Astellas. X.J. Mu: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. K.A. Ching: Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Pfizer. J. Pu: Travel/Accommodation/Expenses, Full/Part-time employment: Roche; Full/Part-time employment: Pfizer. S. Roychoudhury: Full/Part-time employment: Pfizer. C.B. Davis: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. A. di Pietro: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. P. Grivas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Biocept; Research grant/Funding (institution): Bavarian Nordic; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational unbranded activity with Bristol-Myers Squibb (2017): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Driver; Research grant/Funding (institution): Debiopharm; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: EMD Serono; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Exelixis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Heron Therapeutics; Research grant/Funding (institution): Immunomedics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Mirati Therapeutics; Research grant/Funding (institution): Oncogenex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: QED Therapeutics; Honoraria (institution): KureIT; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genzyme. All other authors have declared no conflicts of interest.