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Treatment with mobocertinib (Exkivity) led to clinically meaningful benefits with a manageable safety profile in patients with previously treated EGFR exon 20 insertion mutation-positive metastatic non-small cell lung cancer (NSCLC), researchers found.

The primary endpoint of confirmed objective response rate (ORR) by independent review committee (IRC) was 28% with the oral tyrosine kinase inhibitor among platinum-pretreated patients (PPP) and 25% in a single-arm extension cohort (EXCLAIM), reported Caicun Zhou, MD, PhD, of Shanghai Pulmonary Hospital in China, and colleagues.

ORR by investigator assessment was 35% and 32%, respectively, they noted in .

Mobocertinib "may serve as a potential treatment option in this patient population, which has a high unmet medical need," the authors wrote.

As for secondary endpoints, the median progression-free survival was 7.3 months in both groups, median duration of response was 17.5 months in the PPP group and not estimable in the EXCLAIM group, median overall survival was 24 months and not reached, respectively, and confirmed disease control rate was 78% and 76%, respectively.

Regarding safety, the most common adverse events (AEs) in both cohorts were diarrhea and rash, with diarrhea being the only grade 3 or 4 treatment-related AE that was reported in more than 10% of patients.

"Mobocertinib appears to have a favorable risk-benefit profile in patients with previously treated EGFR exon 20 insertion mutation-positive metastatic NSCLC," Zhou and team noted.

The FDA agreed with that assessment, granting mobocertinib accelerated approval last month as a second-line treatment for locally advanced or metastatic NSCLC, based on results of the PPP cohort.

For their study, Zhou's group conducted a three-part, open-label, with dose-escalation/dose-expansion cohorts, as well as the EXCLAIM cohort, from June 2016 through data cutoff in November 2020.

The PPP cohort consisted of 114 patients (median age 60, 66% women, 60% Asian) who received mobocertinib 160 mg once daily from the dose-escalation (n=6), dose-expansion (n=22), and EXCLAIM (n=86) cohorts. The EXCLAIM cohort included 96 patients (median age 59, 65% women, 69% Asian), 10 of whom were not platinum pretreated and were excluded from the PPP cohort.

The median number of prior systemic anticancer regimens was two in the PPP cohort and one in the EXCLAIM cohort. At data cutoff, median follow-up was 14.2 months and 13.0 months, respectively.

For the two cohorts, the median time to IRC-assessed confirmed response was 1.9 months. Responses were observed in all prespecified subgroups, with no significant differences in ORR between subgroups.

Patients in the EXCLAIM cohort demonstrated improved NSCLC symptom scores, with clinically meaningful improvements in dyspnea, coughing, and chest pain.

In the PPP cohort, 17% of patients discontinued treatment due to AEs, the most common of which were diarrhea (4%), nausea (4%), vomiting (2%), decreased appetite (2%), and stomatitis (2%). Dose reductions due to an AE occurred in 25%, and included diarrhea (11%), nausea (5%), fatigue (3%), maculopapular rash (3%), and vomiting (3%). Twelve patients had AEs leading to death within 30 days after the last dose.

In the EXCLAIM cohort, 10% of patients discontinued treatment because of AEs, including diarrhea and nausea (both 2%). Dose reduction due to an AE occurred in 22%, including diarrhea (9%), fatigue (3%), and nausea (3%). Eight patients had AEs leading to death within 30 days of the last dose

One event -- cardiac failure in a platinum-pretreated patient from EXCLAIM -- was considered treatment related.

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