FDA’s Rybrevant Approval ‘A Step Forward’ For Group of Patients With Non-Small Cell Lung Cancer


The FDA’s recent approval of Rybrevant marks the first targeted therapy for a certain group of patients with non-small cell lung cancer, according to an expert at NYU Langone Health’s Perlmutter Cancer Center.

The Food and Drug Administration’s (FDA) recent approval of Rybrevant (amivantamab-vmjw) provides patients with non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations a potential new treatment opportunity, according to an expert at NYU Langone Health’s Perlmutter Cancer Center.

“EGFR exon 20 insertion mutant lung cancer has been a difficult disease to treat,” Dr. Joshua Sabari, a thoracic medical oncologist at the Perlmutter Cancer Center, said in an interview with CURE®. “Unfortunately, until recently, there were no FDA-approved targeted therapies (for this disease).”

Typically, Sabari noted, the standard of care for the first-line treatment of these patients has consisted of platinum-based chemotherapy combinations. However, according to Sabari, response rates with those therapies are relatively low and the duration of response is quite short. For those patients whose disease failed to respond to the first-line treatment, the second-line standard of care would then be docetaxel-based regimens.

“This approval of (Rybrevant) is the first EGFR-targeted therapy to be approved for people with EGFR exon 20 mutation positive non-small cell lung cancer post platinum doublet chemotherapy,” he said. “(Rybrevant is) also the first bispecific antibody approved in lung cancer.”

The approval, Sabari highlighted, is a step forward for patients whose disease harbors an EGFR exon 20 insertion mutation.

“This is the first drug to show clinical activity in this subset of patients with EGFR exon 20 mutation,” he said. “So, in patients who have growth of their cancer on standard chemotherapy that contains platinum agents, this is now the standard of care in that setting. I hope that in the future, this drug will move to the frontline setting, potentially in combination with chemotherapy or other agents. But clearly, this is an opportunity for patients who've had a mutation that in the past has not been successfully drugged with targeted therapy.”

Potential Side Effects

Rybrevant is associated with a unique side effect profile that is well manageable, according to Sabari. On the first day of treatment, he explained, patients would receive a small dose of the drug. If the patient experiences some form of a side effect — which could include an infusion-related reaction, fever, chills or rash — the medicine would be stopped. The rest of the dose, he noted, would then be administered on the second day of therapy.

“We've seen that by giving a small dose on day one, the rate of infusion reaction is high,” he said. “But on the second day, the rate of the reaction is about less than 1%.”

Sabari also noted that treatment has been associated with some EGFR-mediated side effects such as rash and diarrhea, but that those were low (less than 10%) compared to an EGFR tyrosine kinase inhibitor (approximately 60%).

“The key things to look out for in patients on this therapy is the first day infusion-related reaction which can be mitigated and commonly does not occur again on the second day or subsequent therapy, and then to look out for some of the more common EGFR and MET (mesenchymal epithelial transition factor receptor)-mediated toxicities such as swelling of the lower extremities,” he said.


Treatment with Rybrevant induced a 40% response rate. Sabari explained how that would translate to 40 out of 100 patients experiencing a significant regression of their disease, which he said constitutes a high rate of stability. Moreover, approximately 74% of patients had an ongoing or durable stability of their disease. Patients also achieved a median duration of response of approximately 11.1 months, which according to Sabari is “a significant number for this patient population.”

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