The U.S. FDA recently approved Janssen’s Rybrevant (ingredient: amivantamab) as the first targeted therapy for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
In Korea, researchers are testing a combination therapy mixing Rybrevant with Yuhan Corp.’s Leclaza (lazertinib).
Rybrevant targets both EGFR and MET receptor, also known as hepatocyte growth factor receptor (HGFR). The drug has proved effective in NSCLC patients with various EGFR mutations.
NSCLC with exon 20 mutation is the third-most common type of EGRF mutation, after exon 19 and exon 21, but no treatment has been developed to target it so far.
According to the American Cancer Society (ACS), NSCLC accounts for 80-85 percent of all lung cancer, and 2-3 percent accompanies EGFR exon 20 insertion mutation.
Rybrevant’s overall response rate (ORR) in 81 patients who had prior-platinum chemotherapy was 40 percent. The median duration of response was 11.1 months, and 63 percent of the patients’ duration of response was at least six months.
Rybrevant's most common adverse reactions were rash, injection-related reactions, skin infections around the fingernails and toenails, muscle and joint pain, shortness of breath, and fatigue.
The FDA said patients with symptoms of interstitial lung disease should suspend the use of Rybrevant and discontinue the drug permanently if interstitial lung disease is confirmed.
Also, patients taking Rybrevant should limit sun exposure during treatment and for two months after treatment, the FDA said.
The FDA warned that Rybrevant could cause vision problems and fetal harm in pregnant women. Therefore, physicians should check the pregnancy status of patients with reproductive potential before starting treatment, it added.
The FDA also authorized Guardant360 CDx, a companion diagnostic for Rybrevant, on the same day.
“Advances in precision oncology continue to facilitate drug development, allowing diseases like lung cancer to be subset into biomarker-defined populations appropriate for targeted therapies,” said Julia Beaver, chief of medical oncology in the FDA’s Oncology Center of Excellence.
“With today’s approval, for the first time, patients with NSCLC with EGFR exon 20 insertion mutations will have a targeted treatment option.”
Researchers are exploring Rybrevant’s potential not only as a monotherapy but a combo therapy with Leclaza.
Results from the phase-1b CHRYSALIS study will be released at the upcoming online meeting of the American Society for Clinical Oncology (ASCO 2021) from June 4 to June 8.
The study evaluated the effect of Rybrevant+Leclaza therapy in patients who developed resistance after taking Tagrisso (osimertinib).
According to the study’s abstract released prior to ASCO 2021, researchers administered the combo therapy to 45 NSCLC patients with EGFR exon 19 deletion or L858R mutation who developed resistance after taking Tagrisso. One patient had complete remission (CR), 15, partial remission (PR), and the objective response rate reached 36 percent.
Biomarker analyses showed that 9 out of 10 patients with an H score of 400 or higher responded to the treatment for EGFR and MET mutations in immunohistochemistry (IHC).
However, researchers said they needed additional studies to predict the response rate of the Rybrevant+Leclaza combo based on IHC.