FDA Approves Rybrevant for Locally Advanced, Metastatic Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung Cancer

Image Credit: Adobe Stock Images/Crystal light

The FDA has approved Johnson & Johnson’s (J&J) Rybrevant (amivantamab-vmjw) in combination with chemotherapy (carboplatin and pemetrexed) to treat locally advanced or metastatic epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). The treatment is indicated for patients with exon 19 deletions or L858R substitution mutations and whose disease has progressed after EGFR tyrosine kinase inhibitor therapy. According to the company, this regulatory action marks the first time that a targeted second-line regimen reduced the risk of disease progression by more than 50%.¹

“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, MD, PhD, oncologist, Cancer Care Centers of Brevard, in a press release. “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.”

Approval was based on results of the Phase III MARIPOSA-2 trial, a randomized, open-label study that evaluated the efficacy and safety of two combination regimens of Rybrevant with chemotherapy, with one including Lazcluze. In the trial, 657 patients were randomly assigned to receive either Rybrevant with chemotherapy, Rybrevant with Lazcluze and chemotherapy, or chemotherapy alone. The dual primary endpoints of the study were to compare progression-free survival (PFS) assessed by blinded independent central review (BICR) or each experimental arm to chemotherapy alone. Secondary endpoints included objective response as assessed by BICR, duration of response (DoR), overall survival (OS), time to subsequent therapy, PFS and intracranial PFS.

Results found that the combination therapy demonstrated a 52% reduction in disease progression or death compared to chemotherapy alone, with a median PFS of 6.3 months in the combination group compared to 4.2 months in the solo chemotherapy group. Additionally, the overall response rate for the combination was 53% compared with 29% in the chemotherapy cohort.

Rybrevant was discontinued in 11% patients due to serious adverse events (AEs). In patients who received Rybrevant in combination with chemotherapy, common AEs included rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, decreased appetite, musculoskeletal pain, and COVID-19. Fatal AEs occurred in 2.3% of patients in this group, including respiratory failure, sepsis, and ventricular fibrillation. Serious but not fatal AEs were reported in 32% of patients in this group, such as thrombocytopenia, sepsis, and pulmonary embolism.¹

According to the World Cancer Research Fund International, lung cancer is the most common form of the disease in men and the second most common in women. In 2022, there were 2,480,675 new cases of lung cancer reported worldwide with 1,817,469 deaths. In the United States, the total number of new cases was 226,033, with 127,653 deaths.² The American Cancer Society estimates that anywhere from 80% to 85% of all lung cancers are NSCLC, with small-cell lung cancer making up an estimated 15% of total cases. Although the disease mainly occurs in people over the age of 65 years, it can be diagnosed in a small number of people under 45 years of age.³

“The progression-free survival benefits seen in the MARIPOSA-2 study are exciting,” said Andrea Ferris, president, CEO, LUNGevity Foundation, in the press release. “It is good to see new therapeutic options like the combination of Rybrevant and chemotherapy helping to address unmet needs impacting individuals with EGFR-mutated lung cancer, with the potential for positive change, which gives hope to more patients and their families.”

References

1. 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. J&J. September 19, 2024. Accessed September 20, 2024. https://www.jnj.com/media-center/press-releases/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

2. Lung cancer statistics. WCRF. Accessed September 20, 2024. https://www.wcrf.org/cancer-trends/lung-cancer-statistics/

3. Key Statistics for Lung Cancer. American Cancer Society. Accessed September 20, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html