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Lookup NU author(s): Professor Alastair GreystokeORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Authors; Published by the American Association for Cancer Research. PURPOSE: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase Ib) and confirmed objective response (phase Ib/II). RESULTS: In phase Ib, urothelial carcinoma and NSCLC cohorts received avelumab 800 mg (n = 13 and n = 6, respectively) or 1,200 mg (n = 6 each) + chemotherapy. In evaluable patients with urothelial carcinoma treated with avelumab 800 or 1,200 mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT occurred in the NSCLC cohort. In phase II, 35 additional patients with urothelial carcinoma received avelumab 1,200 mg + chemotherapy. Across all treated patients, safety profiles were similar irrespective of avelumab dose. Objective response rates (95% confidence internal) with avelumab 800 or 1,200 mg + chemotherapy, respectively, across phase Ib/II, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0% (11.8-88.2) and 33.3% (4.3-77.7) in NSCLC. CONCLUSIONS: Preliminary efficacy and safety findings with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with previous studies of similar combination regimens. Conclusions about clinical activity are limited by small patient numbers. SIGNIFICANCE: This phase Ib/II trial evaluated avelumab (immune checkpoint inhibitor) administered concurrently with standard first-line chemotherapy in patients with advanced urothelial carcinoma or advanced nonsquamous NSCLC without actionable mutations. Efficacy and safety appeared consistent with previous studies of similar combinations, although patient numbers were small.
Author(s): Wheatley DA, Berardi R, Climent Duran MA, Tomiak A, Greystoke AP, Joshua AM, Arkenau H-T, Geczi L, Corbacho JG, Paz-Ares LG, Hussain SA, Petruzelka L, Delmonte A, Chappey C, Masters JC, Michelon E, Murphy DA, Mwewa S, Cesari R, Doger de Speville B
Publication type: Article
Publication status: Published
Journal: Cancer Research Communications
Year: 2024
Volume: 4
Issue: 6
Pages: 1609-1619
Online publication date: 28/06/2024
Acceptance date: 24/04/2024
Date deposited: 15/07/2024
ISSN (electronic): 2767-9764
Publisher: American Association for Cancer Research
URL: https://doi.org/10.1158/2767-9764.CRC-23-0459
DOI: 10.1158/2767-9764.CRC-23-0459
PubMed id: 38669053
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