Amivantamab With Lazertinib Can Reduce Risk of Disease Progression By 30% in Patients With NSCLC

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Compared to osimertinib alone, first-line treatment with amivantamab plus lazertinib was also shown to improve progression-free survival and have an increased duration of response.

Data from the phase 3 MARIPOSA (NCT04487080) study demonstrates that amivantamab-vmjw (Rybrevant; Janssen Pharmaceutical) in combination with lazertinib (Leclaza; Johnson & Johnson) compared to osimertinib (Tagrisso; AstraZeneca) resulted in a 30% reduction in the risk of disease progression or death in first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with either epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution. The data were presented at the 2023 European Society of Medical Oncology (ESMO) Congress.

Close-up of non-small cell carcinoma in lung

Image credit: Saiful52 | stock.adobe.com

This randomized phase 3 study’s primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), overall response rate, second PFS, and intracranial PFS. The investigators enrolled 1074 patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations were randomly assigned to receive either amivantamab in combination with lazertinib, and either osimertinib or lazertinib alone.

Amivantamab is a bispecific antibody that targets EGFR and MET with immune cell-directing activity indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy. It is also used as first-line treatment for patients with NSCLC in combination with chemotherapy (carboplatin-pemetrexed).

"Despite advances in EGFR-mutated NSCLC treatment, novel targeted therapies and regimens are needed to address resistance and disease progression, which are nearly inevitable with current treatments," said presenting author Byoung Chul Cho, MD, PhD, medical oncologist and professor in the division of medical oncology at Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Republic of Korea, in a press release.

The results show that compared to osimertinib alone, amivantamab in combination with lazertinib reduced the risk of disease progression or death by 30% in patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. At a median follow-up of 22 months, the median PFS for patients treated with amivantamab plus lazertinib was 23.7 months compared to osimertinib, which was 16.6 months.

Further, secondary endpoints demonstrated consistent and clinically meaningful benefits for the combination of amivantamab plus lazertinib versus osimertinib. Compared to patients who received only osimertinib, the median duration of response was significantly longer for patients receiving amivantamab and lazertinib, with a 9-month improvement (25.8 vs. 16.8 months, respectively).

"[Amivantamab] is a first-in-class bispecific antibody that targets major oncogenic driver pathways and, when combined with lazertinib, may lead to a more complete and synergistic response against the tumor," said Peter Lebowitz, MD, PhD, global therapeutic area head, oncology, Janssen Research & Development, LLC. "The prolonged duration of [PFS] and favorable trend in OS observed in the MARIPOSA study show the potential of [amivantamab] in combination with lazertinib to transform first-line treatment in EGFR-mutated NSCLC."

Patients who received treatment with amivantamab with lazertinib mostly reported adverse events (AEs) that were grade 1 or 2 in severity, and the most common grade 3 or higher treatment-related AEs were rash and paronychia. Amivantamab plus lazertinib had higher rates of EGFR- and MET-related AEs (eg, hypoalbuminemia and peripheral edema), venous thromboembolism, and diarrhea compared to osimertinib. The safety profile of the combination of amivantamab with lazertinib was consistent with the safety profiles of the individual treatments. Further, any instances of toxicity were primarily manageable with dose interruptions and reductions.

"With the combination of [amivantamab] and lazertinib in the MARIPOSA study, [PFS] was significantly improved in patients with previously untreated EGFR-mutated NSCLC compared to osimertinib. These results support the potential of this [amivantamab] combination to be a future standard of care," Cho said in the press release.

Reference

Johnson & Johnson. Landmark Phase 3 MARIPOSA Study Shows RYBREVANT® (amivantamab-vmjw) Plus Lazertinib Resulted in 30 Percent Reduction in Risk of Disease Progression or Death Compared to Osimertinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer. News release. October 23, 2023. Accessed October 25, 2023. https://www.prnewswire.com/news-releases/landmark-phase-3-mariposa-study-shows-rybrevant-amivantamab-vmjw-plus-lazertinib-resulted-in-30-percent-reduction-in-risk-of-disease-progression-or-death-compared-to-osimertinib-in-patients-with-egfr-mutated-non-small-cell-lung-301964599.html?tc=eml_cleartime

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