Amivantamab/lazertinib combo shows promise in EGFR-mutated NSCLC

Among nonsmall cell lung cancer (NSCLC) patients with mutations spanning exons 18 to 21, combination treatment with amivantamab and lazertinib induces high rates of response, reports a study presented at the recent 2022 European Society for Medical Oncology Asia Congress (ESMO Asia 2022).

“Amivantamab plus lazertinib demonstrated durable antitumour activity in advanced NSCLC with atypical EGFR mutations. Robust activity was seen in both treatment-naïve and postafatinib patients,” said lead author Byoung Chul Cho of the Yonsei Cancer Center in South Korea.

“The key take-home message of this abstract is that among a rare patient population with few treatment options, amivantamab plus lazertinib demonstrated encouraging antitumour activity in a majority of patients,” he added.

Researchers conducted an interim analysis of the ongoing CHRYSALIS-2 trial, an open-label study including an expansion phase assessing amivantamab and lazertinib in patients with advanced NSCLC patients harbouring atypical mutations other than exon 20 insertions. Amivantamab was given at 1,050-mg intravenous doses weekly during the first cycle and every other week thereafter; lazertinib was taken orally at 240-mg doses every day.

Patients who had received at least two prior lines of therapy, including at least one first- or second-generation tyrosine kinase inhibitor (TKI), were eligible for enrolment. The study’s primary outcome was treatment response, which was assessed based on the RECIST criteria.

By the data cutoff on 8 June 2022, 40 patients (median age 64 years, 47.5 percent women) had response data available for analysis, of whom two had undergone two prior lines of therapy. The most common mutation was a G719X substitution in exon 19, detected in 60.0 percent of participants. Most patients harboured compound mutations. [ESMO Asia 2022, abstract 322MO]

The best antitumour response achieved was partial response, documented in 60 percent (n=24) of the study sample. Moreover, 30 patients had available data for the analysis of overall response rate (ORR), from whom researchers calculated an ORR of 53 percent.

Of note, partial response was apparent across several atypical mutations, including exon 20 S768I, exon 21 L861Q, exon 18 E709K, G719X, and L861R.

Prior treatment exposure likewise did not seem to significantly impact the efficacy of amivantamab/lazertinib. Of the 21 treatment-naïve patients, 71 percent saw a ≥30-percent reduction in tumour lesions and yielded an ORR of 59 percent. Among those who had been treated with afatinib, 50 percent demonstrated a ≥30-percent reduction in lesion burden, with an ORR of 50 percent.

As of the clinical cutoff, 78 percent (n=31) of participants were still receiving amivantamab/lazertinib, with the median duration of treatment of 5.95 months among the 21 responders. Median duration of response, as assessed by the investigators, was not evaluable. Patients demonstrated response lasting for at least 6 months.

In terms of safety, the investigators found that amivantamab/lazertinib had a tolerability profile consistent with what had already been established in prior studies. Eight (15 percent) and 10 (19 percent) patients underwent dose reductions due to adverse events associated with amivantimab and lazertinib, respectively. Three patients (6 percent) had to drop out of the study due to toxicities.