FDA Approves Johnson & Johnson’s Rybrevant and Lazcluze for Advanced Non-Small Cell Lung Cancer

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The FDA has approved Johnson & Johnson’s (J&J) combination of Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) as a first-line, chemotherapy-free treatment for advanced non-small cell lung cancer (NSCLC) with specific epidermal growth factor receptor (EGFR) mutations. J&J states that the treatment is the first multitargeted regimen to surpass Tagrisso (osimertinib) in efficacy, according to results of the Phase III MARIPOSA trial, in which the combination reduced the risk of disease progression or death by 30% and extended progression-free survival (PFS) by an additional seven months compared with Tagrisso.¹

"This approval is a crucial development for patients with EGFR-mutated NSCLC, who have faced significant unmet needs for far too long," said Jill Feldman, lung cancer survivor, co-founder, EGFR Resisters, a patient advocacy group, in a press release. "Having witnessed firsthand the remarkable evolution in lung cancer treatment, this profoundly important milestone brings a novel therapeutic approach to patients and their families. I'm thrilled that more patients can now experience the progression-free survival benefits seen in the MARIPOSA study."

The randomized MARIPOSA trial evaluated Rybrevant in combination with Lazcluze versus Tagrisso and versus Lazcluze as a monotherapy in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or substitution mutations. The primary endpoint of the study was PFS as assessed by blinded independent central review. Secondary endpoints included overall survival, overall response rate, duration of response (DOR), second PFS, and intracranial PFS.

The results, which were published in The Journal of Clinical Oncology last year, also found that the median DOR was nine months longer with the combination therapy compared to Tagrisso (25.8 months versus 16.7 months).¹

"The unique combination of Rybrevant and Lazcluze demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC as shown with the MARIPOSA study," said Alexander Spira, MD, PhD, FACP, director, Virginia Cancer Specialists Research Institute, study investigator, in the press release. "Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over [Tagrisso]. This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex."

Common adverse events (AEs) associated with the combination therapy included rash, nail toxicity, infusion-related reactions, musculoskeletal pain, stomatitis, edema, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. Serious AEs occurred in 49% of patients who received the combination therapy. Further, fatal AEs were reported in 7% of patients, including sepsis, respiratory failure, pneumonia, myocardial infarction, sudden death, cerebral infarction, pulmonary embolism, interstitial lung disease/pneumonitis, acute respiratory distress syndrome, and cardiopulmonary arrest. The safety profile of Rybrevant in combination with Lazcluze was consistent with previous studies.

According to J&J, around 1.8 million people die annually as a result of lung cancer, with approximately 80% to 85% of all cases being NSCLC. Current statistics show that between 29% and 35% of patients with EGFR-mutated NSCLC never receive second-line therapy, due to disease progression and lack of treatment options. With current standard of care of tyrosine kinase inhibitor monotherapy, the five-year survival rate is less than 20%.¹

"Building on more than three decades of oncology innovation, we are uniquely positioned to build best-in-class treatments where survival rates have remained stagnant for years," said Jennifer Taubert, EVP, worldwide chairman, innovative medicine, Johnson & Johnson. "Rybrevant plus Lazcluze establishes a new benchmark in the advanced first-line setting, and we look forward to bringing this new chemotherapy-free treatment regimen to patients."

Reference

1. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. PR Newswire. August 20, 2024. Accessed August 20, 2024. https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-approved-in-the-us-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer-302226047.html#:~:text=RARITAN%2C%20N.J.%2C%20Aug.%2020,non-small%20cell%20lung%20cancer%20