The JAVELIN Bladder Medley Trial: Avelumab-Based Combinations as First-Line Maintenance in Advanced Urothelial Carcinoma

Abstract

Results from JAVELIN Bladder 100 established avelumab (anti–PD-L1) first-line maintenance as the standard-of-care treatment for patients with advanced urothelial carcinoma (UC) that has not progressed with first-line platinum-based chemotherapy. We describe the design of JAVELIN Bladder Medley (NCT05327530), an ongoing phase II, multicenter, randomized, open-label, parallel-arm, umbrella trial. Overall, 252 patients with advanced UC who are progression-free following first-line platinum-based chemotherapy will be randomized 1:2:2:2 to receive maintenance therapy with avelumab alone (control group) or combined with sacituzumab govitecan (anti–Trop-2/topoisomerase inhibitor conjugate), M6223 (anti-TIGIT) or NKTR-255 (recombinant human IL-15). Primary end points are progression-free survival per investigator and safety/tolerability of the combination regimens. Secondary end points include overall survival, objective response and duration of response per investigator, and pharmacokinetics.

Plain language summary

Urothelial cancer develops in the urinary tract, which contains the parts of the body that move urine from the kidneys to outside of the body. Urothelial cancer is called advanced when it has spread outside of the urinary tract. Chemotherapy is often the first main treatment given to people with advanced urothelial cancer. Avelumab is an immunotherapy drug that can help the body’s immune system find and destroy cancer cells. Results from a trial called JAVELIN Bladder 100 looked at avelumab maintenance treatment, which is given after chemotherapy. The trial showed that avelumab maintenance treatment helped people with advanced urothelial cancer live longer than people who were not treated with avelumab. Avelumab also helped people have a longer time without their cancer getting worse. Avelumab is the only approved maintenance treatment available for people with advanced urothelial cancer that has not worsened after chemotherapy. The JAVELIN Bladder Medley trial will assess whether avelumab maintenance treatment given in combination with other anticancer drugs can help people with advanced urothelial cancer live longer and have a longer time without their cancer getting worse compared with avelumab alone. Researchers will also look at the side effects people have when they receive avelumab alone or combined with the other anticancer drugs in this trial. Results will show whether the benefit of avelumab maintenance treatment can be improved by combining avelumab with other anticancer drugs. People started joining this trial in August 2022. Results will be reported in the future.

Clinical Trial Registration: NCT05327530 (ClinicalTrials.gov)

Graphical abstract

Infographic

Infographic: A PDF version of this infographic is available as supplemental material.

Tweetable abstract

Recruiting! JAVELIN Bladder Medley: a phase II umbrella trial exploring novel combinations with avelumab as #1LMaintenanceTherapy for advanced #UrothelialCarcinoma after 1L chemotherapy (NCT05327530).

Keywords::

• advanced urothelial carcinoma
• avelumab
• JAVELIN Bladder Medley
• M6223
• maintenance
• NKTR-255
• phase II trial
• sacituzumab govitecan

Supplementary data

An infographic accompanies this paper. To view or download this infographic in your browser please click here: https://www.tandfonline.com/doi/suppl/10.2217/fon-2023-0492

Author contributions

All authors drafted, critically reviewed or revised the manuscript for important intellectual content. All authors reviewed the final version and agreed with the content and approved of the decision to submit.

Acknowledgments

The authors thank the patients and their families, investigators, co-investigators and the study teams at each of the participating centers. For further information about the study, please contact either US Medical Information ([phone]; [email protected]) or Communication Center ([phone]; [email protected]).

Financial & competing interests disclosure

This trial is sponsored by Merck (CrossRef Funder ID: 10.13039/100009945). 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.

Financial & competing interests disclosure

Sacituzumab govitecan is provided by Gilead Sciences and NKTR-255 is provided by Nektar Therapeutics. J Hoffman-Censits has served in consulting or advisory roles for Seattle Genetics (Seagen); and reports other disclosures for Ikena Oncology, QED Therapeutics and Seagen. P Grivas has served in consulting or advisory role for 4D Pharma PLC, Aadi Bioscience, Asieris Pharmaceuticals, AstraZeneca, Astellas Pharma, Boston Gene, Bristol Myers Squibb, CG Oncology, Dyania Health, Exelixis, Fresenius Kabi, Genentech/Roche, Gilead Sciences, Guardant Health, G1 Therapeutics, ImmunityBio, Infinity Pharmaceuticals, Janssen, Lucence Health, Merck, Mirati Therapeutics, MSD, Pfizer, PureTech, QED Therapeutics, Regeneron Pharmaceuticals, Seattle Genetics, Silverback Therapeutics, Strata Oncology, UroGen; and his institution has received research funding from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, Merck, Mirati Therapeutics, MSD, Pfizer and QED Therapeutics. T Powles has served in consulting or advisory roles for Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Merck, MSD, Novartis, Pfizer, Roche and Seattle Genetics; has received travel and accommodation expenses from AstraZeneca, Ipsen, MSD, Pfizer and Roche; and has received institutional research funding from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Johnson & Johnson, Merck, MSD, Novartis, Pfizer, Roche and Seattle Genetics. J Hawley has served in consulting or advisory roles for Seagen, and has received institutional research funding from AstraZeneca, Bristol Myers Squibb, Dendreon and Regeneron. K Tyroller reports employment by EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, and stock and other ownership interests in Merck. S Seeberger, S Guenther and N Jacob report employment by Merck Healthcare KGaA, Darmstadt, Germany. K Tadjalli Mehr reports employment by Merck Healthcare KGaA, Darmstadt, Germany, and stock and other ownership interests in Merck. N M Hahn has received institutional research funding from Astex, AstraZeneca, Bristol Myers Squibb, Genentech, HTG Molecular Diagnostics, Incyte, Inovio, MSD, Pieris and Seattle Genetics; has served in consulting or advisory roles for BioGears, Boehringer Ingelheim, Champions Oncology, CicloMed, Ferring, Genentech, GlaxoSmithKline, Guidepoint Global, Health Advances, Incyte, Janssen, KeyQuest Health, Merck, Mirati, MSD, Pfizer, Protara Therapeutics, RemeGen, Seattle Genetics, TransMed and Verity Pharma; and has received honoraria from Bladder Cancer Academy, Creative Educational Concepts, and the Large Urology Group Practice Association. 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.

Writing disclosure

Medical writing support was provided by Amy Davidson of Clinical Thinking, and was funded by Merck.

Ethical conduct of research

The protocol, any protocol amendments and all other relevant documents are approved by an institutional review board or independent ethics committee at each participating institution before patient enrolment is initiated. The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. In addition, informed consent has been/will be obtained by investigators from the participants involved.

Data sharing statement

Any requests for data by qualified scientific and medical researchers for legitimate research purposes will be subject to Merck’s (CrossRef Funder ID: 10.13039/100009945) Data Sharing Policy. All requests should be submitted in writing to Merck’s data sharing portal (www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html). When Merck has a co-research, co-development, or co-marketing or co-promotion agreement, or when the product has been out-licensed, the responsibility for disclosure might be dependent on the agreement between parties. Under these circumstances, Merck will endeavor to gain agreement to share data in response to requests.