Avelumab (Anti-PD-L1) in Platinum-Resistant/Refractory Ovarian Cancer: JAVELIN Ovarian 200 Phase III Study Design

Abstract

Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

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Keywords::

• avelumab
• ovarian cancer
• PD-L1

Author’s contributions

All authors met the criteria for authorship set forth by the International Committee of Medical Journal Editors, and were involved in conception, preparation, and approval of the manuscript.

Acknowledgements

The authors would like to thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers.

Financial & competing interests disclosure

The JAVELIN Ovarian 200 trial discussed in this manuscript is sponsored by Pfizer Inc., New York, NY, USA, and is part of an alliance between Pfizer Inc. and Merck KGaA, Darmstadt, Germany. E Pujade-Lauraine has acted in a consultant/advisory role for AstraZeneca, Pfizer, and Roche and has received travel, accommodation, or expenses from AstraZeneca, Pfizer, and Roche. BJ Monk has acted in a consultant/advisory role for Amgen, AstraZeneca, Clovis, Gradalis, Immunogen, Insys, Mateon, Merck KGaA, Pfizer, Precision Oncology, and Tesaro, and has provided speaker services for AstraZeneca, Clovis, and Tesaro. K Fujiwara has acted in a consultant/advisory role for AstraZeneca, Chugai-Roche, Eisai, GSK, Lilly, Merck & Co, and Pfizer and has provided speaker services for Chugai-Roche, Daiichi-Sankyo, Jannsen, Kyowahakko-Kirin, Lilly, Nippon Kayaku, Novartis, Ono Pharmaceutical, Taiho, Yakult, and Zeria Pharma. K Fujiwara has received research grants from Advanced Oncotherapy, AstraZeneca, Chungai-Roche, Daiichi-Sankyo, Eisai, GSK, ImmunoGen, Kaken-Seiyaku, Lilly, Merck & Co, Ono Pharmaceutical, Pfizer, Shionogi, Taiho, and Zeria Pharma. SS Dychter and G Devgan are employees of Pfizer, Inc. SS Dychter holds stock in Fate Therapeutics and Halozyme Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing assistance was provided by Amy Davidson at ClinicalThinking, Inc, Hamilton, NJ, USA, and was funded by Merck KGaA, Darmstadt, Germany and Pfizer Inc, New York, NY, USA.

Notes

ECOG: Eastern Cooperative Oncology Group; NCI CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; PLD: Pegylated liposomal doxorubicin; RECIST: Response Evaluation Criteria In Solid Tumors; ULN: Upper limit of normal.

ICR: Independent central review; ir: Immune related; PFS: Progression-free survival; PK: Pharmacokinetic; RECIST: Response Evaluation Criteria In Solid Tumors.

Additional information

Funding

The JAVELIN Ovarian 200 trial discussed in this manuscript is sponsored by Pfizer Inc., New York, NY, USA, and is part of an alliance between Pfizer Inc. and Merck KGaA, Darmstadt, Germany. E Pujade-Lauraine has acted in a consultant/advisory role for AstraZeneca, Pfizer, and Roche and has received travel, accommodation, or expenses from AstraZeneca, Pfizer, and Roche. BJ Monk has acted in a consultant/advisory role for Amgen, AstraZeneca, Clovis, Gradalis, Immunogen, Insys, Mateon, Merck KGaA, Pfizer, Precision Oncology, and Tesaro, and has provided speaker services for AstraZeneca, Clovis, and Tesaro. K Fujiwara has acted in a consultant/advisory role for AstraZeneca, Chugai-Roche, Eisai, GSK, Lilly, Merck & Co, and Pfizer and has provided speaker services for Chugai-Roche, Daiichi-Sankyo, Jannsen, Kyowahakko-Kirin, Lilly, Nippon Kayaku, Novartis, Ono Pharmaceutical, Taiho, Yakult, and Zeria Pharma. K Fujiwara has received research grants from Advanced Oncotherapy, AstraZeneca, Chungai-Roche, Daiichi-Sankyo, Eisai, GSK, ImmunoGen, Kaken-Seiyaku, Lilly, Merck & Co, Ono Pharmaceutical, Pfizer, Shionogi, Taiho, and Zeria Pharma. SS Dychter and G Devgan are employees of Pfizer, Inc. SS Dychter holds stock in Fate Therapeutics and Halozyme Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing assistance was provided by Amy Davidson at ClinicalThinking, Inc, Hamilton, NJ, USA, and was funded by Merck KGaA, Darmstadt, Germany and Pfizer Inc, New York, NY, USA.