Amivantamab in combination with Lazertinib showed efficacy in NSCLC

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ONCOLOGY

Medical writer: Connie TANG | Last updated: 22 November 2021 | In: Lung Cancer, Oncology, Targeted Therapies

Article Keywords

osimertinib, T790M, lung cancer, amivantamab, lazertinib, tyrosine kinase inhibitor, NSCLC, EGFR

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer.¹ Epidermal growth factor receptor (EGFR) activating mutations occur in 40-55% of Asian lung adenocarcinoma patients.² However, resistance mutations such as the T790M mutation are often observed in patients undergoing treatment with first, second, and third generation EGFR-tyrosine kinase inhibitors (TKIs).³ Newer drugs are needed to treat drug resistance, and double-targeting by using an EGFR-directed monoclonal antibody plus an EGFR-TKI may help to overcome tumour escape mechanisms.

Amivantamab is an EGFR and mesenchymal epithelial transition factor (MET) bispecific antibody that may overcome the acquired resistance to approved TKI.⁴ Lazertinib is a third-generation EGFR-TKI active against resistance mutations including T790M.⁵ Efficacy data of amivantamab as monotherapy and in combination with lazertinib in advanced EGFR-mutant NSCLC patients were presented at the 2021 ESMO Congress and summarised below.

The ongoing open-label CHRYSALIS trial evaluated the efficacy and safety of amivantamab in patients with advanced EGFR mutant NSCLC who had progressed on osimertinib.⁶ There were 121 patients receiving amivantamab mono-treatment and 45 patients receiving combo-treatment of amivantamab plus lazertinib.⁶ EGFR/MET-based resistance was found in 85% of mono patients and 38% of combo patients.⁶ Amivantamab demonstrated antitumour activity with an overall response rate (ORR) of 19% and 36% in the mono group and combo group, respectively.⁶ The clinical benefit rate (CBR) measured 64% in the combo group; 16% higher compared with the 48% CBR observed in the mono group, showing additive benefits of the simultaneous inhibition of EGFR by the monoclonal antibody plus the EGFR-TKI even in patients without molecular selection post-osimertinib failure.⁶ The median duration of response was 5.9 months in mono and 9.6 months in combo group.⁶ Amivantamab demonstrated a consistent safety profile with previous studies.⁶

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Preliminary results of the phase 1/1b CHRYSALIS-2 study investigating the combination of amivantamab and lazertinib in patients with progression after osimertinib and platinum doublet chemotherapy were also presented.⁷ Eligible patients harboured EGFR Exon19del or L858R mutations and had disease progression after osimertinib and platinum chemotherapy (target population) or were more heavily-pretreated.⁷ Patients received a recommended dose of 1050 mg intravenous injection of amivantamab (1400 mg, ≥80 kg) and 240 mg oral lazertinib.⁷ A total of 116 patients were enrolled, with evaluable responses in 28 out of 59 patients in the target population and 45 out of 57 patients in the heavily-pretreated population.⁷ The partial response (PR) and ORR were 43% and 32% in the target population, while the PR of 15% and ORR of 13% were reported in the heavily-pretreated population.⁷ In the target population, 17 patients remained on treatment at a median follow-up of 3.7 months, with 10 patients having a PR and 7 stable disease.⁷ No new safety signals were identified.⁷

In conclusion, amivantamab plus lazertinib exhibited promising anti-tumour activity by exerting synergistic inhibition of EGFR-TKI resistant in NSCLC patients harbouring EGFR mutations and who were pretreated with a TKI – including osimertinib – and chemotherapy.

Reference

American Cancer Society. Available online. https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Last accessed: 10 September 2021

Rocco D et al. Expert Opin Pharmacother. 2021;0(0):1-8.

Günther M, et al. Angew Chem Int Ed. 2016, 55.36: 10890-4.

Park K et al. J Clin Oncol. Published online August 2, 2021:JCO2100662.

Ahn M-J et al. Lancet Oncol. 2019;20(12):1681-90.

Leighl NB et al. 1192MO. Presented at 2021 ESMO Congress. Available at: https://cslide.ctimeetingtech.com/esmo2021/attendee/confcal/session/calendar?q=amivantamab

Shu CA et al. 1193MO. Presented at 2021 ESMO Congress. Available at: https://cslide.ctimeetingtech.com/esmo2021/attendee/confcal/session/calendar?q=amivantamab

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).