OA04.03 Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations

Abstract

on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival analyzed on an intention-totreat basis. Adverse events were assessed according to treatment received. Results: Between 22 May 2015 and 12 March 2018, 503 patients were randomly allocated to treatment. Median overall survival was 13.6 months (95% CI, 10.9e16.5) for the 251 patients allocated to docetaxel and 16.2 months (95% CI, 14.4e19.0) for the 252 patients allocated to nab-paclitaxel (hazard ratio, 0.85; 95.2% CI, 0.68e1.07). Median progression-free survival was 4.2 months (95% CI, 3.9e5.0) for the nab-paclitaxel group versus 3.4 months (95% CI, 2.9e4.1) for the docetaxel group (hazard ratio, 0.76; 95% CI, 0.63e0.92; p¼0.0042). The objective response rate was 29.9% (95% CI, 24.0e36.2) for the nab-paclitaxel group and 15.4% (95% CI, 10.9e20.7) for the docetaxel group (p¼0.0002), and it showed a significant improvement for nabpaclitaxel versus docetaxel regardless of tumor histology. Adverse events of grade 3 included febrile neutropenia (55 [22%] of 249 patients in the docetaxel group versus 5 [2%] of 245 patients in the nab-paclitaxel group) and peripheral sensory neuropathy (2 [1%] versus 24 [10%], respectively). Conclusion: The trial showed that nabpaclitaxel was noninferior to docetaxel in terms of overall survival. Nab-paclitaxel should thus be considered a standard treatment option for previously treated patients with advanced NSCLC.

Amivantamab in EGFR Exon 20 Insertion–Mutated Non–Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study

“…Treatmentrelated AEs of diarrhea in 90% of patients (21% grade 3-4) and rash in 45% were reported. 28 The safety profile of amivantamab was consistent with expected on-target toxicities associated with inhibition of EGFR and MET. IRRs were frequently observed but were low grade, primarily limited to the first infusion, and rarely occurred with further dosing.…”

“…Presented at the ASCO 2020 Annual Meeting, virtual, May 29-31, 2020, and updated data were presented at the International Association for the Study of Lung Cancer World Conference on Lung Cancer (WCLC) 2020 Annual Meeting, virtual, January [28][29][30][31]2021.…”

EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy

“…Although poziotinib showed disappointing results (low ORR and limiting toxicities) [21,22], mobocertinib recently obtained breakthrough therapy designation from the U.S. FDA after a phase I/IItrial and expansion cohort (PFS = 7.3 months and ORR = 26%) [23]. Phase II EXCLAIM confirmed PFS = 7.3 months, and quite similarly, ORR = 23% [24]. The EXCLAIM-2 phase III trial, evaluating mobocertinib vs. platinum-based chemotherapy in treatment-naïve patients, is ongoing (NCT04129502).…”

Amivantamab: A Potent Novel EGFR/c-MET Bispecific Antibody Therapy forEGFR-mutated Non-small Cell Lung Cancer

“…40,41 In the most recently published cohort of 114 platinum pre-treated patients with EGFR ex20ins tumours, confirmed ORR was 26% with median DOR of 17.5 months and median PFS of 7.3 months. 42 Similarly to other anti-EGFR therapies, mobocertinib 160 mg had significant toxicities and was associated with diarrhoea in 90% of patients (including grade ≥3 diarrhoea in 22%), rash in 45% of patients, and required treatment discontinuation in 17% of patients. 42 Neither amivantamab nor mobocertinib appear to have significant central nervous system penetration, which are limitations compared with osimertinib for common EGFR mutations.…”

“…42 Similarly to other anti-EGFR therapies, mobocertinib 160 mg had significant toxicities and was associated with diarrhoea in 90% of patients (including grade ≥3 diarrhoea in 22%), rash in 45% of patients, and required treatment discontinuation in 17% of patients. 42 Neither amivantamab nor mobocertinib appear to have significant central nervous system penetration, which are limitations compared with osimertinib for common EGFR mutations. 43 Osimertinib has been investigated in EGFR ex20ins tumours based on the excellent activity against classical TKI-sensitive EGFR mutations as well as preclinical data that it can bind ex20ins-mutated EGFR despite the presence of the rigid C-helix that sterically hinders the binding of first-and second-generation EGFR TKIs.…”