CHMP Recommends Johnson & Johnson's Rybrevant for Pre-treated Advanced NSCLC

Johnson & Johnson’s (J&J) Rybrevant (amivantamab) has received a positive nod from the European Medicines Agency’s human medicines committee for use as a combination therapy in treating a specific group of advanced non-small cell lung cancer (NSCLC) patients.

This bispecific antibody has been recommended by the Committee for Medicinal Products for Human Use (CHMP) in combination with carboplatin and pemetrexed chemotherapy. The targeted group includes adults suffering from advanced NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R (L858R) substitution mutations, particularly after previous therapies, including an EGFR tyrosine kinase inhibitor (TKI), have failed.

Lung cancer remains the leading cause of cancer-related deaths globally, with NSCLC making up approximately 85% of all lung cancer diagnoses. Among these, patients with EGFR ex19del or EGFR L858R mutations face a particularly grim outlook with limited treatment options following disease progression on AstraZeneca’s TKI Tagrisso (osimertini).

Rybrevant is designed to directly inhibit EGFR on the cell surface, thereby preventing tumor growth. It is already approved in the EU for treating advanced NSCLC in certain adults with activating EGFR exon 20 insertion mutations. The latest endorsement by the CHMP is based on encouraging results from the MARIPOSA-2 study, a late-stage trial that assessed Rybrevant plus chemotherapy in patients with locally-advanced or metastatic EGFR ex19del or L858R substitution NSCLC whose disease had progressed after treatment with Tagrisso.

The MARIPOSA-2 study achieved its primary objective, demonstrating that the combination of Rybrevant and chemotherapy reduced the risk of disease progression or death by 52% compared to chemotherapy alone. Moreover, the treatment combo showed an objective response rate of 64%, significantly higher than the 36% observed with chemotherapy alone.

Kiran Patel, vice president of clinical development for solid tumors at J&J Innovative Medicine, noted that Rybrevant has already shown positive outcomes in treating other EGFR mutations. Patel expressed optimism for making the drug available to more patients with common EGFR mutations who have experienced disease progression on Tagrisso.

This recommendation follows closely on the heels of Rybrevant's recent approval by the European Commission. Just a month ago, Rybrevant was cleared for use in combination with carboplatin and pemetrexed chemotherapy as a first-line treatment for advanced NSCLC in adults with EGFR exon 20 insertion mutations.

The positive recommendation from the CHMP adds another layer of hope for patients with these specific genetic mutations, offering an additional treatment avenue after the failure of previous therapies. As J&J looks forward to the next steps, the potential for Rybrevant to improve outcomes for a broader patient population seems promising.