| Autor: |
Benjamin J. Solomon, M.B.B.S., PhD, Ibiayi Dagogo-Jack, MD, Se-Hoon Lee, MD, Michael J. Boyer, M.B.B.S., PhD, Suresh S. Ramalingam, MD, Enric Carcereny, MD, Enriqueta Felip, MD, PhD, Ji-Youn Han, MD, PhD, Toyoaki Hida, PhD, Brett G.M. Hughes, M.B.B.S., Sang-We Kim, MD, PhD, Makoto Nishio, MD, PhD, Takashi Seto, MD, Tatsuro Okamoto, MD, PhD, Xiaoxi Zhang, PhD, Jean-Francois Martini, PhD, Erjian Wang, MD, PhD, Steven De Beukelaer, MD, Todd M. Bauer, MD |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
JTO Clinical and Research Reports, Vol 5, Iss 7, Pp 100685- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2666-3643 |
| DOI: |
10.1016/j.jtocrr.2024.100685 |
| Popis: |
Introduction: The JAVELIN Lung 101 phase 1b/2 trial evaluated avelumab (immune checkpoint inhibitor) combined with lorlatinib or crizotinib (tyrosine kinase inhibitors) in ALK-positive or ALK-negative advanced NSCLC, respectively. Methods: Starting doses of lorlatinib 100 mg once daily or crizotinib 250 mg twice daily were administered with avelumab 10 mg/kg every 2 weeks. Primary objectives were assessment of maximum tolerated dose (MTD) and recommended phase 2 dose in phase 1 and objective response rate in phase 2. Primary end points were dose-limiting toxicity (DLT) and confirmed objective response per Response Evaluation Criteria in Solid Tumors, version 1.1. Results: In the avelumab plus lorlatinib group (ALK-positive; n = 31; 28 in phase 1b; three in phase 2), two of 28 assessable patients (7%) had DLT, and the MTD and recommended phase 2 dose was avelumab 10 mg/kg every 2 weeks plus lorlatinib 100 mg once daily. In the avelumab plus crizotinib group (ALK-negative; n = 12; all phase 1b), five of 12 assessable patients (42%) had DLT, and the MTD was exceeded with avelumab 10 mg/kg every 2 weeks plus crizotinib 250 mg twice daily; alternative crizotinib doses were not assessed. Objective response rate was 52% (95% confidence interval, 33%–70%) with avelumab plus lorlatinib (complete response, 3%; partial response, 48%) and 25% (95% confidence interval, 6%–57%) with avelumab plus crizotinib (all partial responses). Conclusions: Avelumab plus lorlatinib treatment in ALK-positive NSCLC was feasible, but avelumab plus crizotinib treatment in ALK-negative NSCLC could not be administered at the doses tested. No evidence of increased antitumor activity was observed in either group. ClinicalTrials.gov identifier: NCT02584634 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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