Avelumab first-line maintenance is a recommended treatment option for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy (PBC). The JAVELIN Bladder Medley phase II trial is investigating the efficacy and safety of maintenance treatment with avelumab combined with other antitumor agents versus avelumab monotherapy. We report an interim analysis of avelumab plus sacituzumab govitecan (SG) versus avelumab monotherapy.
Patients with la/mUC without progression after first-line PBC were randomized 2 : 1 to receive avelumab (800 mg every 2 weeks) plus SG (10 mg/kg on days 1 and 8 of 21-day cycles) or avelumab monotherapy (800 mg every 2 weeks). Primary endpoints are investigator-assessed progression-free survival (PFS) and safety. For PFS and overall survival (OS), data in the avelumab monotherapy arm were extended per protocol using propensity score-weighted JAVELIN Bladder 100 data.
At data cut-off (16 September 2024), 38/74 patients (51.4%) in the avelumab plus SG arm and 10/37 patients (27.0%) in the avelumab monotherapy arm were still receiving study treatment. Median PFS with avelumab plus SG versus avelumab monotherapy was 11.17 versus 3.75 months, respectively [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31-0.76; prespecified efficacy boundary: HR ≤ 0.60]. OS data were immature; median OS was not reached versus 23.75 months, respectively (HR 0.79, 95% CI 0.42-1.50). In patients treated with avelumab plus SG or avelumab monotherapy, any-grade treatment-related adverse events (TRAEs) occurred in 97.3% versus 63.9% (grade ≥3 in 69.9% versus 0%), respectively.
In patients with la/mUC without progression after first-line PBC, PFS was prolonged with avelumab plus SG versus avelumab monotherapy as maintenance treatment. TRAEs were more frequent with the combination and were consistent with known safety profiles of SG and avelumab. Combining avelumab with anti-Trop-2 antibody-drug conjugates may be a promising strategy to improve patient outcomes in la/mUC.
Annals of oncology : official journal of the European Society for Medical Oncology. 2025 May 30 [Epub ahead of print]
J Hoffman-Censits, M Tsiatas, P M-H Chang, M Kim, L Antonuzzo, S J Shin, G Gakis, N Blais, S H Kim, A Smith, J A Arranz Arija, Y L Su, F Zagouri, M Maruzzo, C Tournigand, F Forget, A Schneider, K Tyroller, N Jacob, P Grivas, B P Valderrama
Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institutions, Baltimore, USA; Department of Urology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institutions, Baltimore, USA. Electronic address: ., Department of Medical Oncology, Athens Medical Center, Marousi, Greece., Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Biopharmaceutical Science, National Yang Ming Chiao Tung University, Taipei, Taiwan., Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea., Clinical Oncology Unit, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea., University Clinic and Polyclinic of Urology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany., Hematology-Oncology Division, University of Montreal Health Centre (CHUM), Montreal, Canada., Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Icon Cancer Centre, Adelaide, Australia., Department of Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid, Spain., Department of Hematology Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan., Department of Clinical Therapeutics, 'Alexandra' General Hospital of Athens, Athens, Greece., Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy., Department of Medical Oncology, AP-HP, Hôpital Henri Mondor, Créteil, France., Centre Hospitalier de l'Ardenne, Libramont-Chevigny, Belgium., Merck Healthcare KGaA, Darmstadt, Germany., EMD Serono Research & Development Institute, Inc., Billerica, USA, an affiliate of Merck KGaA., University of Washington, Fred Hutchinson Cancer Center, Seattle, USA., Hospital Universitario Virgen del Rocio, Seville, Spain.