Updates on the Safety and Efficacy of Amivantamab and Lazertinib Combination Therapy for EGFR-Mutated Non-small Cell Lung Cancer - European Medical Journal

Updates on the Safety and Efficacy of Amivantamab and Lazertinib Combination Therapy for EGFR-Mutated Non-small Cell Lung Cancer

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THE UPCOMING International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), August 6th-9th, Vienna, Austria, will feature Janssen-sponsored presentations that provide updates on data from clinical trials. The trials evaluate the safety and efficacy of amivantamab and lazertinib combination therapy plus carboplatin–pemetrexed chemotherapy in patients with relapsed/refractory, epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Anticipation of the findings spotlight the need for continued research to improve precision medicine, given the current few treatment options available for this patient cohort.

NSCLC is a lung cancer sub-type that accounts for approximately 85% of European lung cancer diagnoses. Pro-cancerous, activating mutations in the tyrosine kinase transmembrane EGFR are common in NSCLC. Therefore, drug development to target these EGFR mutations is vital in advancing therapeutic strategies for patients with EGFR-mutated NSCLC. Amivantamab is a monoclonal antibody that directly targets EGFR exon 20 activating insertion mutations, while lazertinib is an oral EGFR tyrosine kinase inhibitor that acts selectively on EGFRs with activating mutations. There are several clinical trials investigating amivantamab, lazertinib, and carboplatin–pemetrexed chemotherapy, including Phase I/Ib CHRYSALIS-2, Phase I CHRYSALIS, Phase III MARIPOSA, and Phase III MARIPOSA-2.

CHRYSALIS-2 is a Phase I/Ib, open-label, multi-centre study evaluating the safety, anti-tumour efficacy, and tolerability of lazertinib as both a monotherapy and a combination therapy with amivantamab for adult patients with advanced, EGFR-mutated NSCLC. One faction of the trial enrolled 20 patients to evaluate the efficacy and safety profile of amivantamab and lazertinib combination therapy alongside carboplatin–pemetrexed chemotherapy. These patients had received a median of two previous lines of treatment, had refractory or relapsed NSCLC with EGFR exon 19 deletion mutations or L858R activating mutations, and were followed up for a median of 7.1 months. During the follow-up period, the overall response rate was 50% (95% confidence interval: 27–73). Of the 20 patients included, one-quarter discontinued secondary to disease progression or adverse chemotherapy events. These events were in line with the known safety profiles for each individual therapeutic, and no new safety or toxicity concerns of treatment using amivantamab and lazertinib with carboplatin–pemetrexed were identified. The data from CHRYSALIS-2 highlight the potential for combination therapy in the treatment of EGFR-mutated NSCLC and support ongoing research. As a result, recruitment has begun for Phase III of the MARIPOSA-2 study to evaluate amivantamab and lazertinib combination therapy plus carboplatin–pemetrexed in patients who have previously failed treatment with osimertinib, a tyrosine kinase inhibitor.

Further to this, updated data from Phase I of the CHRYSALIS study have shown that all 20 treatment-naïve patients with EGFR-mutated NSCLC, treated with either amivantamab as monotherapy or in combination with Lazertinib, displayed a partial response (100% overall response rate; 95% confidence interval: 83.3–100.0) after a 7-month median follow-up time. After 22.3 months, 70% of these patients remained on therapy and were free of disease progression. The safety profile of amivantamab and lazertinib combination therapy is consistent with previous safety reports, and no new safety concerns were discovered.

The ongoing Phase III MARIPOSA study evaluates amivantamab and lazertinib against osimertinib and against lazertinib alone for advanced, untreated EGFR-mutated NSCLC. Presentations at the IASLC will share these trial updates and discuss the use of next-generation sequencing to identify patients who may benefit from specific treatments.

These findings suggest potential future treatment options for advanced relapsed/refractory EGFR-mutated NSCLC, a subtype in which few treatment options are available. Catherine Taylor, Vice President, EMEA Medical Affairs, Therapy Area Strategy at Janssen Europe, Middle East, and Africa, highlighted that these trials support their research aim to “improve outcomes for people with non-small cell lung cancer in Europe, especially those whose disease is characterised by specific genetic mutations and who tend to be underserved by the current standard of care.”

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