NEW YORK – The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) on Monday recommended approval of Johnson & Johnson's subcutaneous formulation of its EGFR and MET bispecific antibody Rybrevant (amivantamab) for advanced non-small cell lung cancer patients harboring certain EGFR mutations.
The CHMP recommended subcutaneous Rybrevant with the EGFR inhibitor Lazcluze (lazertinib) as a first-line treatment for advanced NSCLC patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations. The committee also recommended subcutaneous Rybrevant monotherapy for advanced NSCLC patients with activating EGFR exon 20 insertion mutations after failure on platinum-based therapy. The European Commission will consider the CHMP's recommendation and decide whether to approve these indications for NSCLC patients in Europe.
The recommendations were based on results from the Phase III PALOMA-3 trial, which compared subcutaneous Rybrevant with intravenous Rybrevant, both in combination with Lazcluze, in previously treated EGFR-mutant advanced or metastatic NSCLC. The trial showed that subcutaneous Rybrevant was non-inferior to intravenous Rybrevant by two pharmacokinetics endpoints.
Subcutaneous Rybrevant also demonstrated similar efficacy to intravenous Rybrevant, with an overall response rate of 30 percent with the subcutaneous version versus 33 percent with intravenous Rybrevant. With the subcutaneous formulation, there was a five-fold reduction in the rate of infusion-related reactions in the PALOMA-3 trial compared to the intravenous formulation, 13 percent versus 66 percent, respectively.
"The subcutaneous formulation of amivantamab offers an improved treatment experience for patients, reducing administration time from hours to minutes and substantially lowering rates of infusion-related reactions compared to the currently approved intravenous therapy," Silvia Novello, professor of medical oncology at San Luigi Hospital in Orbassano, Italy, which is part of the University of Turin, said in a statement.
In Europe, intravenous Rybrevant is already approved for first-line treatment of advanced NSCLC with certain EGFR mutations with Lazcluze or with chemotherapy, as a monotherapy treatment for advanced NSCLC with activating EGFR exon 20 insertion mutations who failed platinum-based therapy, and in combination with chemo for advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, after failure of prior therapy.
In December, the US Food and Drug Administration sent a complete response letter to J&J for its application seeking approval for subcutaneous Rybrevant, citing observations during a standard preapproval inspection at a manufacturing facility.