Cancer treatment and research communications · 2026
Phase 1/2 trial of brigatinib plus panitumumab in patients with osimertinib-resistant EGFR-mutated non-small cell lung cancer harboring EGFR C797S mutation.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Izumi Hiroki, Sakamoto Tomohiro, Uchibori Ken, Nishino Kazumi, Sakakibara-Konishi Jun, Katayama Ryohei, Nomura Shogo, Matsumoto Shingo, Udagawa Hibiki, Shibata Yuji, Sakai Tetsuya, Nosaki Kaname, Zenke Yoshitaka, Yoh Kiyotaka, Niho Seiji, Goto Koichi
Аннотация
BACKGROUND: Osimertinib is a standard treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). The EGFR C797S mutation is one of the most common resistant mechanisms to osimertinib. Based on our preclinical data, the safety and efficacy of brigatinib combined with panitumumab was evaluated in phase 1/2 study.
METHOD: This open-label phase 1/2 study enrolled patients with osimertinib-resistant EGFR-mutated NSCLC, with phase 1 dose escalation part, followed by phase 2 dose expansion part. The primary endpoint was the incidence of dose-limiting toxicities for phase 1 part, and objective response rate for phase 2 part.
RESULT: A total of 5 patients were enrolled between Dec 2020 and Jun 2021. Patients had received a median of 4 (range, 1-7) prior lines of treatment, no patient received prior immune checkpoint inhibitors. Median washout period from last dose of osimertinib was 10 days (range, 2-393). Three (60%) patients experienced early onset pulmonary event (EOPE) (grade [Gr] 2, n = 1; Gr 3, n = 2), all of which occurred during brigatinib monotherapy period. All cases with EOPE improved with brigatinib interruption for Gr 2, and systemic corticosteroid treatment for Gr 3. The efficacy to study treatment were PD in all 5 patients, with median progression-free survival of 1.7 months (95% CI, 1.2 to 3.4). Exploratory ctDNA analysis showed the decrease in relative allele frequency (C797S/exon19 deletion) between pre- and post-treatment (n = 3).
CONCLUSION: The clinical development of this combination strategy was discontinued, as brigatinib treatment was not feasible in patients with advanced EGFR-mutated NSCLC resistant to osimertinib.
METHOD: This open-label phase 1/2 study enrolled patients with osimertinib-resistant EGFR-mutated NSCLC, with phase 1 dose escalation part, followed by phase 2 dose expansion part. The primary endpoint was the incidence of dose-limiting toxicities for phase 1 part, and objective response rate for phase 2 part.
RESULT: A total of 5 patients were enrolled between Dec 2020 and Jun 2021. Patients had received a median of 4 (range, 1-7) prior lines of treatment, no patient received prior immune checkpoint inhibitors. Median washout period from last dose of osimertinib was 10 days (range, 2-393). Three (60%) patients experienced early onset pulmonary event (EOPE) (grade [Gr] 2, n = 1; Gr 3, n = 2), all of which occurred during brigatinib monotherapy period. All cases with EOPE improved with brigatinib interruption for Gr 2, and systemic corticosteroid treatment for Gr 3. The efficacy to study treatment were PD in all 5 patients, with median progression-free survival of 1.7 months (95% CI, 1.2 to 3.4). Exploratory ctDNA analysis showed the decrease in relative allele frequency (C797S/exon19 deletion) between pre- and post-treatment (n = 3).
CONCLUSION: The clinical development of this combination strategy was discontinued, as brigatinib treatment was not feasible in patients with advanced EGFR-mutated NSCLC resistant to osimertinib.