Wheatley, D.A. orcid.org/0000-0002-1919-5114, Berardi, R. orcid.org/0000-0002-9529-2960, Climent Duran, M.A. orcid.org/0000-0001-7523-0212 et al. (17 more authors) (2024) First-line avelumab plus chemotherapy in patients with advanced solid tumors: results from the phase Ib/II JAVELIN chemotherapy medley study. Cancer Research Communications, 4 (6). pp. 1609-1619. ISSN 2767-9764
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license. (http://creativecommons.org/licenses/by/4.0/) |
Keywords: | Humans; Antibodies, Monoclonal, Humanized; Female; Middle Aged; Male; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Carboplatin; Gemcitabine; Deoxycytidine; Cisplatin; Pemetrexed; Adult; Carcinoma, Transitional Cell; Aged, 80 and over; Urologic Neoplasms |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Aug 2024 12:05 |
Last Modified: | 07 Aug 2024 12:05 |
Status: | Published |
Publisher: | American Association for Cancer Research (AACR) |
Refereed: | Yes |
Identification Number: | 10.1158/2767-9764.crc-23-0459 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215625 |