Rybrevant (amivantamab-vmjw) plus standard of care approved in the U.S. as first and only targeted regimen to cut risk of disease progression by more than half in second-line EGFR-mutated advanced lung cancer
Johnson & Johnson announced that the FDA approved Rybrevant (amivantamab-vmjw) in combination with standard of care chemotherapy (carboplatin and pemetrexed) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth actor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).
“Rybrevant plus chemotherapy may address the most common mechanisms of treatment resistance to third generation EGFR TKIs, such as osimertinib, in the first line,” said Martin Dietrich*, M.D., Ph.D., Oncologist, Cancer Care Centers of Brevard. “This multitargeted combination extended progression-free survival and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients.”
The five-year survival rate is less than 20 percent for all people with advanced EGFR-mutated NSCLC. Acquired resistance mechanisms after TKI monotherapy are diverse and polyclonal, making targeted therapy at progression more difficult, thus limiting the efficacy of targeted therapies at progression. Adding immunotherapy to chemotherapy has also failed to demonstrate clinically meaningful improvements.
The FDA approval is based on results from the Phase III MARIPOSA-2 (NCT04988295) study evaluating the efficacy and safety of Rybrevant in combination with chemotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations after disease progression on or after osimertinib. Results showed Rybrevant plus chemotherapy reduced the risk of disease progression or death (progression-free survival [PFS]) by 52 percent vs. chemotherapy alone, the study’s primary endpoint. The median PFS for patients receiving Rybrevant plus chemotherapy was 6.3 months, compared to 4.2 months for chemotherapy alone. Additionally, Rybevant plus chemotherapy showed a confirmed overall response rate (ORR) of 53 percent compared to 29 percent with chemotherapy alone.
Amivantamab-vmjw (Rybrevant ) in combination with chemotherapy is the only National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) Category 1 treatment option for patients with EGFR-mutated NSCLC progressing on osimertinib who are symptomatic with multiple lesions.
The safety profile of Rybrevant in combination with chemotherapy was consistent with the established profiles of the individual treatments. Permanent discontinuation of Rybrevant due to adverse reactions occurred in 11 percent of patients.
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