FDA Approves J&J's Rybrevant Combo for EGFR-Mutated NSCLC

The US Food and Drug Administration (FDA) has approved Johnson & Johnson's (J&J) Rybrevant (amivantamab-vmjw) as part of a combination treatment for certain patients with non-small cell lung cancer (NSCLC). This new approval specifically targets adults with locally advanced or metastatic NSCLC, featuring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. Such patients must have experienced disease progression despite previous treatment with an EGFR tyrosine kinase inhibitor (TKI).

NSCLC represents up to 85% of all lung cancer cases, with EGFR mutations being one of the most prevalent genetic alterations driving the disease. Advanced EGFR-mutated NSCLC has a poor prognosis, with less than a 20% five-year survival rate. One of the main challenges in treating this type of cancer is the development of resistance mechanisms after initial TKI therapy, complicating further treatment efforts.

Rybrevant, a bispecific antibody, functions by directly inhibiting EGFR on the cell surface, thereby halting tumor growth. It is already approved in the United States for specific cases, such as NSCLC with EGFR exon 20 insertion mutations. The recent FDA endorsement of this therapy was based on favorable outcomes from the MARIPOSA-2 study. This late-stage trial assessed the efficacy of Rybrevant combined with chemotherapy in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC, who had previously undergone treatment with AstraZeneca’s third-generation EGFR TKI, Tagrisso (osimertinib).

The MARIPOSA-2 study demonstrated that the Rybrevant combination significantly reduced the risk of disease progression or death by 52% compared to chemotherapy alone, thereby meeting the primary endpoint of the study. Patients receiving Rybrevant in combination with chemotherapy had a median progression-free survival of 6.3 months, contrasted with 4.2 months for those on chemotherapy alone. Additionally, the overall response rate with the Rybrevant regimen was confirmed at 53%, compared to 29% for chemotherapy-only patients.

Kiran Patel, Vice President of Clinical Development for Solid Tumors at J&J Innovative Medicine, emphasized the importance of this milestone. Patel stated, “This milestone reinforces Rybrevant as an important treatment option for patients with EGFR-mutated NSCLC who continue to face high unmet needs after disease progression on or after TKI therapy. Patients need and deserve effective, targeted approaches across all lines of therapy.”

The approval of Rybrevant in combination with chemotherapy comes just a month after another significant FDA approval for J&J. Rybrevant, when combined with J&J’s third-generation EGFR TKI, Lazcluze (lazertinib), was endorsed as a first-line treatment for adults with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.

These regulatory advancements underscore the ongoing effort to enhance the therapeutic landscape for NSCLC patients with EGFR mutations, aiming to provide more effective, targeted treatment options to improve survival outcomes and quality of life.