Early Phase Data Demonstrates Efficacy of Amivantamab/Lazertinib Combination in NSCLC

New data demonstrated the safety and efficacy of amivantamab-vmjw plus lazertinib and platinum-based chemotherapy in patients with relapsed or refractory, EGFR-mutant non–small cell lung cancer.

New data from the phase 1b/2 CHRYSALIS-2 study (NCT04077463) demonstrated the safety and efficacy of amivantamab-vmjw (Rybrevant) plus lazertinib and platinum-based chemotherapy in patients with relapsed or refractory, EGFR-mutant non–small cell lung cancer (NSCLC). Additional updates will be presented at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), according to Janssen.1

Amivantamab and lazertinib with carboplatin and pemetrexed elicited an overall response rate of 50% (95% CI, 27%-73%) after a median follow-up of 7.1 months. Additionally, 15 of the 20 patients remained on treatment. Enrolled participants in this cohort of the trial had received a median of 2 prior lines of therapy including osimertinib (Tagrisso; n = 14), gefitinib (Iressa; n = 3), afatinib (Gilotrif; n = 3), and platinum-based chemotherapy (n = 5). The most common treatment-emergent adverse events (AEs) were neutropenia (85%), rash (75%), infusion-related reaction and stomatitis (60%), fatigue and paronychia (50% each), and thrombocytopenia and nausea (40% each). No new safety signals or additional toxicities were observed in this cohort.

Amivantamab received accelerated approval from the FDA in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGRF exon 20 insertion mutations who have disease progression on or after platinum-based chemotherapy.

CHRYSALIS-2 enrolled patients with EGFR exon 19 deletion mutations or L858R activating mutations to one of 2 investigational cohorts: amivantamab in combination with the third-generation EGFR TKI lazertinib and platinum-based chemotherapy or lazertinib plus amivantamab alone.

Data from a treatment-naïve cohort of patients who received amivantamab in combination with lazertinib of the phase 1 CHRYSALIS study (NCT02609776) will also be presented at the meeting, according to Janssen. Patients in this cohort had either an EGFR exon 19 deletion (n = 11) or L858R mutation (n = 9) with 50% of patients having comutations in the TP53 gene. All treated patients (n = 20) responded.

Further, at a median follow-up of 22.3 months, 70% (n = 14) of patients were progression free, and the median duration of response and median progression-free survival were not reached. At the last data cutoff on June 1, 2022, the median follow-up and treatment duration was 28 months, 60% of patients (n = 12) remained on treatment progression free.

Amivantamab with lazertinib had a consistent safety profile with previous reports and AEs of grade 3 or higher were reported in 7 patients (35%). A dose reduction of either amivantamab or lazertinib occurred in 7 patients, 5 of which were due to rash. One patient discontinued treatment after a treatment-related AE of interstitial lung disease.

“Patients with relapsed/refractory NSCLC with EGFR mutations currently have few treatment options,” Alexander Spira, MD, PhD, FACP, CEO and clinical director of NEXT Oncology Virginia and study investigator said in a news release. “For them, the promise of precision medicine has the potential to change the trajectory of their disease. The data we’ve seen with the combination of amivantamab with lazertinib and chemotherapy further demonstrate the potential of this treatment regimen for these patients, and we are optimistic about future study to improve outcomes for those with EGFR-positive NSCLC.”

Several phase 3 confirmatory trials for these regimens are underway including the MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib in the frontline setting treatment and MARIPOSA-2 (NCT04988295) evaluating the combination of amivantimab, Lazertinib, and platinum-based chemotherapy in patients with EGFR-mutated NSCLC after disease progression on or after osimertinib.

The IASLC 2022 WCLC will also feature new data from Janssen on the utility of next-generation sequencing testing in identifying patients with NSCLC who may benefit from targeted treatment.

Reference

Janssen announces new data supporting safety and efficacy of Rybrevant and lazertinib combination for patients with non-small cell lung cancer and EGFR mutations. News release. Janssen Pharmaceutical companies of Johnson & Johnson. July 26, 2022. Accessed July 29, 2022. https://bit.ly/3S8OiCz