Rybrevant in Combination with Lazertinib Shows Promise in Non–Small Cell Lung Cancer

Amivantamab-vmjw (Rybrevant; Janssen Pharmaceutical Companies) in combination with lazertinib, carboplatin, and pemetrexed had an overall response rate of 50% for patients with relapsed/refractory non–small cell lung cancer (NSCLC) and third-generation epidermal growth factor receptor (EGFR) mutations, with 15 of 20 individuals remaining on the treatment, according to a statement from the company.

The findings of the phase 1b/2 CHRYSALIS-2 cohort evaluating the safety and tolerability of the combination of amivantamab-vmjw with the EGFR tyrosine kinase inhibitor, lazertinib, and the platinum-based chemotherapy, carboplatin, for individuals with relapsed/refractory NSCLC, will be presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer.

CHRYSALIS-2 is ongoing clinical trial evaluating amivantamab-vmjw in combination with lazertinib in individuals with advanced NSCLC with EGFR exon 19 deletion mutations or L858R activating mutations. Another cohort in the study is evaluating the combination of amivantamab-vmjw and lazertinib with carboplatin and pemetrexed.

The results of the amivantamab-vmjw, lazertinib, carboplatin, and pemetrexed cohort will also be presented at the conference in a mini oral presentation. Individuals who were enrolled received a median of 2 prior lines of therapy, including osimertinib, gefitinib, afatinib, and other platinum-based chemotherapy.

There was a median follow-up time of 7.1 months. The safety profile that was observed for this combination was consistent with the previously reported safety profile of each individual agent, and no evidence of new safety signals or additional toxicities were observed.

The most common treatment-emergent adverse event (AEs) included neutropenia, rash, infusion-related reaction and stomatitis, fatigue and paronychia, and thrombocytopenia and nausea.

Janssen is currently recruiting individuals for the phase 3 MARIPOSA-2 study, which will evaluate the combination of amivantamab-vmjw and lazertinib with platinum-based chemotherapy in individuals with EGFR-mutated NSCLC after disease progression on or after osimertinib.

Additionally, data from the treatment-naïve cohort of the phase 1 CHRYSALIS study will be featured in a poster presentation. CHRYSALIS is evaluating the safety, pharmacokinetics, and preliminary efficacy of amivantamab-vmjw as a monotherapy and in combination, including with lazertinib, in individuals with advanced NSCLC with various EGFR mutations. The individuals in this cohort either had NSCLC characterized by EGFR exon 19 deletion or L858R mutation and 50% of individuals had a co-mutation in the TP53 gene.

All 20 individuals had confirmed response and after a median follow-up of 22.3 months, 14 individuals were progression-free and remained on therapy with a median duration of response. Median progression-free survival has not been reached.

Based upon the last data cutoff on June 1, 2022, 12 individuals remained progression-free and on treatment.

The safety profile of the combination of amivantamab-vmjw and lazertinib was consistent with previous reports, and no new safety signals were identified.

Janssen will also share data that highlight the utility of next-generation sequencing testing in identifying individuals with NSCLC who may benefit from targeted treatment in a mini oral presentation during the IASLC 2022 WCLC conference.

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. Johnson and Johnson. July 26, 2022. https://www.jnj.com/janssen-announces-new-data-supporting-safety-and-efficacy-of-rybrevant-and-lazertinib-combination-for-patients-with-non-small-cell-lung-cancer-and-egfr-mutations