Johnson & Johnson’s (J&J) Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) have been approved by the US Food and Drug Administration as a first-line combination treatment for adults with non-small cell lung cancer (NSCLC).
Patients eligible for the chemotherapy-free combination will have locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
The regulator’s decision was supported by positive results from the late-stage MARIPOSA study, in which Rybrevant, an EGFRxMET bispecific antibody, plus Lazcluze, a third-generation EGFR tyrosine kinase inhibitor (TKI), reduced the risk of disease progression or death by 30% compared to AstraZeneca’s own third-generation EGFR-TKI Tagrisso (osimertinib) in this patient population.
The combination was also shown to extend median duration of response by nine months versus Tagrisso, a secondary endpoint of the trial, and the safety profile of Rybrevant plus Lazcluze was consistent with the profiles of the individual treatments.
NSCLC accounts for up to 85% of all lung cancer cases, and alterations in EGFR are among the most common actionable driver mutations in patients with this form of the disease.
Up to 39% of those with EGFR-mutated NSCLC never receive second-line therapy due to disease progression and lack of treatment options, with acquired resistance mechanisms after standard of care TKI monotherapy making subsequent treatment more difficult.
Commenting on the new approval, study investigator Alexander Spira, Virginia Cancer Specialists Research Institute, said: “Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over [Tagrisso].
“This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex.”
The authorisation comes just five months after the FDA approved Rybrevant in combination with carboplatin and pemetrexed chemotherapy for the first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
Rybrevant was also granted traditional approval to treat adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, upgrading the regulator’s May 2021 accelerated approval for the drug in this indication.