Janssen Submits Supplemental Application for Rybrevant in NSCLC

Janssen has submitted to the FDA a supplemental biologics license application (sBLA) for the approval of Rybrevant (amivantamab-vmjw) in combination with chemotherapy to treat patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution. If approved, it would be indicated to treat patients after disease progression on or after Tagrisso (osimertinib).

Non-small-cell lung cancer makes up at about 80% to 85% of all lung cancer cases. The most common mutation in NSCLC is an alternative in EGFR, which is a receptor tyrosine kinase controlling cell growth and division. EGFR ex19del or EGFR L858R substitutions are the most common EGFR mutations. Patients with EGFR ex19del or L858R mutations have a real-world five-year overall survival of 19%.

Kiran Patel, M.D.

“New treatment options are urgently needed in the post-osimertinib setting, where patients continue to face unacceptable survival rates,” Kiran Patel, M.D., vice president, clinical development, solid tumors, Janssen Research & Development, said in a press release.

Rybrevant is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. It received accelerated approval by the FDA in May 2021 to treat adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. In August 2023, Janssen submitted an application for Rybrevant to be used as a first-line treatment with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

The supplemental application for use after Tagrisso is based on data from the phase 3 MARIPOSA-2, which was recently presented at the European Society of Medical Oncology (ESMO) 2023 Congress in October 2023 and published in the Annals of Oncology. MARIPOSA-2 enrolled 657 patients in an open-label study that assessed Rybrevant (with and without lazertinib) and chemotherapy.

Investigators found that Rybrevant given with or without lazertinib and combined with chemotherapy reduced the risk of disease progression or death by 56% and 52%, respectively. Additionally, Rybrevant plus chemotherapy showed an objective response rate of 64% and Rybrevant plus chemotherapy and lazertinib demonstrated an objective response rate of 63%, compared with a response rate of 36% with chemotherapy alone.

Serious adverse events occurred in 52% of patients receiving Rybrevant plus chemotherapy with lazertinib and 32% of patients treated with Rybrevant plus chemotherapy, compared with 20% of patients who received chemotherapy alone. The incidence of treatment-related adverse events leading to death was low and comparable between all treatment arms. Rates of venous thromboembolism (VTE) were higher in the Rybrevant combinations, mostly grade 1 or 2 with no rrade 5 events.