TY - JOUR
T1 - Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer
T2 - Phase 1b Results from the JAVELIN Solid Tumor Trial
AU - Disis, Mary L.
AU - Taylor, Matthew H.
AU - Kelly, Karen
AU - Beck, J. Thaddeus
AU - Gordon, Michael
AU - Moore, Kathleen M.
AU - Patel, Manish R.
AU - Chaves, Jorge
AU - Park, Haeseong
AU - Mita, Alain C.
AU - Hamilton, Erika P.
AU - Annunziata, Christina M.
AU - Grote, Hans Juergen
AU - Von Heydebreck, Anja
AU - Grewal, Jaspreet
AU - Chand, Vikram
AU - Gulley, James L.
N1 - Funding Information:
KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer Inc, New York, NY. Dr Gulley received research funding from the Center for Cancer Research, National Cancer Institute.
Funding Information:
Additional Contributions: We thank the patients and their families, investigators, coinvestigators, and the study teams at each of the participating centers and at Merck KGaA (Darmstadt, Germany), EMD Serono Research & Development Institute (Billerica, MA; a business of Merck KGaA, Darmstadt, Germany), and IVQIA (Durham, NC). Medical writing support was provided by ClinicalThinking, funded by Merck KGaA and Pfizer.
Funding Information:
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.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060643540&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2018.6258
DO - 10.1001/jamaoncol.2018.6258
M3 - Article
C2 - 30676622
AN - SCOPUS:85060643540
VL - 5
SP - 393
EP - 401
JO - JAMA Oncology
JF - JAMA Oncology
SN - 2374-2437
IS - 3
ER -