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Clinical Trial
. 2019 Mar 1;5(3):393-401.
doi: 10.1001/jamaoncol.2018.6258.

Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial

Mary L Disis  1   2 , Matthew H Taylor  3 , Karen Kelly  4 , J Thaddeus Beck  5 , Michael Gordon  6 , Kathleen M Moore  7 , Manish R Patel  8 , Jorge Chaves  9 , Haeseong Park  10 , Alain C Mita  11 , Erika P Hamilton  12 , Christina M Annunziata  13 , Hans Juergen Grote  14 , Anja von Heydebreck  15 , Jaspreet Grewal  16   17 , Vikram Chand  16   18 , James L Gulley  19
Affiliations
Clinical Trial

Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial

Mary L Disis et al. JAMA Oncol. .

Abstract

Importance: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy.

Objective: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer.

Design, setting, and participants: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018.

Intervention: Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study.

Main outcomes and measures: Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety.

Results: A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred.

Conclusions and relevance: Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer.

Trial registration: ClinicalTrials.gov identifier: NCT01772004.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Disis reported receiving research funding from Celgene, EMD Serono, Epithany, Janssen, Pfizer, and Seattle Genetics; holding stock in Epithany; and being an inventor on patents held by the University of Washington. Dr Taylor reported serving as a consultant or advisor for Blueprint, Bristol-Myers Squibb, Eisai, Loxo, and Novartis; performing speaker services for Bristol-Myers Squibb and Eisai; and receiving travel, accommodation, and expenses from Blueprint, Bristol-Myers Squibb, Eisai, and Loxo. Dr Kelly reported receiving honoraria from Merck & Co.; receiving research funding from AbbVie, Celgene, EMD Serono, Five Prime Therapeutics, Genentech, Lilly, Lycera, Novartis, Regeneron, and Transgene; receiving travel, accommodation, and expenses from ARIAD, AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Lilly, Merck & Co, and Regeneron; and serving as a consultant or advisor for AbbVie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, G1 Therapeutics, Genentech/Roche, Janssen, Lilly, and Regeneron. Dr Gordon reported receiving research funding from AbbVie, Acetylon, Aduro Biotech, Advaxis, Amgen, Array BioPharma, BeiGene, BiolineRx, Calithera Biosciences, CanBas, Celgene, Celldex, Corcept Therapeutics, CytomX Therapeutics, Deciphera, Driver Group, Endocyte, ESSA, Five Prime Therapeutics, Fujifilm, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Halozyme, Hengrui Therapeutics, Inanovate, Incyte, Lilly, MabVax, Macrogenics, MedImmune, Merck Serono, Merrimack, Millennium, Minneamrita Therapeutics, Nektar, Novartis, Novita Pharmaceuticals, OncoMed, Pfizer, Phoenix Biotech, Plexxikon, Proderm IQ, Samumed, Seattle Genetics, Sirtex Medical, Strategia Therapeutics, Syndax, SynDevRx, Tesaro, Tokai Pharmaceuticals, Tolero Pharmaceuticals, Toray Industries, TRACON Pharma, Trovagene, and Verastem; serving as a consultant or advisor for Castle Biosciences, Deciphera, RedHill Biopharma, and TRACON Pharma; and holding stock in Caremission and WCCT Global. Dr Moore reported serving as a consultant or advisor for Advaxis, AstraZeneca, Clovis Oncology, Genentech/Roche, Immunogen, Janssen Oncology, TESARO, and VBL Therapeutics; receiving research funding from Lilly and PTC Therapeutics; and receiving travel, accommodation, and expenses from Genentech/Roche. Dr Patel reported serving as a speaker for Celgene, Exelixis, Genentech/Roche, and Taiho Pharmaceutical. Dr Chaves reported receiving research funding from Calithera Biosciences, Celgene, EMD Serono, Halozyme, Immune Design, Novartis, and Pfizer; and holding stock in Abbott Laboratories, Johnson & Johnson, and Merck & Co. Dr Park reported receiving research funding from Amgen, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Daiichi Sankyo, EMD Serono, Gilead Sciences, Incyte, Lilly, Macrogenics, MedImmune, Medivation, Merck & Co, Millennium, Novartis, Pfizer, Puma Biotechnology, Regeneron, Roche, Taiho Pharmaceutical, and Vertex. Dr Mita reported serving as a speaker for Genentech. Dr Hamilton reported receiving research funding from AbbVie, Acerta Pharma, AstraZeneca, BerGenBio, Boehringer Ingelheim, Cascadian Therapeutics, Curis, eFFECTOR Therapeutics, Eisai, Fujifilm, Genentech/Roche, H3 Biomedicine, Hutchison MediPharma, Immunomedics, Kadmon, Lilly, Lycera, Macrogenics, Mallinckrodt, MedImmune, Medivation, Mersana, Merus, Millennium, Novartis, Nucana, OncoMed, Pfizer, PharmaMar, Radius Health, Rgenix, Stem CentRx, Syndax, Takeda, TapImmune Inc, Tesaro, TetraLogic Pharmaceuticals, Verastem, and Zymeworks; and serving as a consultant or advisor for Cascadian Therapeutics, Flatiron Health, Genentech/Roche, Lilly, and Pfizer. Dr Annunziata reported receiving research funding from Precision Biologics; and holding patents, royalties, or other intellectual property for MaxCyte and Precision Biologics. Dr Grote and Dr von Heydebreck are employees of Merck KGaA. Dr Grewal was an employee of EMD Serono while the study was being performed. Dr Chand was an employee of EMD Serono while the study was being performed; is a current employee of AstraZeneca; and reported holding stock in Bristol-Myers Squibb. Dr Gulley reported receiving research funding from Astellas Medivation, Bavarian Nordic, EMD Serono, NantBioScience Inc, and Pfizer.

Figures

Figure 1.
Figure 1.. Study Flowchart
Figure 2.
Figure 2.. Antitumor Activity of Avelumab
A, Time to and duration of response (n = 12). B, Best change in target lesions from baseline in patients with evaluable data (n = 114). Each bar represents a patient. Dotted lines indicate changes in target lesion size of −30% and +20%. C, Change in target lesions from baseline over time in patients with evaluable data (n = 114). Dotted lines indicate the changes in target lesion size of −30%, 0%, and +20%. Imputed data point is 205.0%.
See this image and copyright information in PMC

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