J&J’s Lung Cancer Combo Outperforms Tagrisso in Survival Rates

Johnson & Johnson has achieved a breakthrough in the treatment of non-small cell lung cancer (NSCLC), with its combination therapy of Rybrevant and Lazcluze demonstrating a clear survival advantage over AstraZeneca’s Tagrisso. The results come from the phase 3 MARIPOSA trial, which involved 1,074 patients with advanced or metastatic NSCLC harboring EGFR exon 19 deletions or L858R substitution mutations.
The study revealed that J&J’s combination therapy could extend overall survival by at least one year beyond Tagrisso’s median survival of three years. While overall survival was a secondary endpoint, it remains the “gold standard endpoint” for patients and physicians, according to Mark Wildgust, Ph.D., J&J’s vice president of oncology global medical affairs. Wildgust highlighted the significance of the findings, stating, “The results really show that we have a new standard of care for patients with EGFR non-small cell lung cancer.”
Tagrisso, a third-generation EGFR tyrosine kinase inhibitor, has been the standard of care for nearly a decade and generated $5.8 billion in sales in 2023. However, the new data from MARIPOSA suggests that J&J’s therapy could challenge its dominance. The FDA approved the Rybrevant-Lazcluze combination in August 2024, and initial data presented at the World Conference on Lung Cancer shortly thereafter showed a 23% reduction in the risk of death compared to Tagrisso.

The dual mechanism of the combination therapy—targeting both EGFR and mesenchymal-epithelial transition (MET) pathways—has been key to its success. By addressing both pathways, the therapy minimizes resistance, a common limitation of single-target treatments. Wildgust noted that “dual targeting of EGFR and MET received less resistance,” adding that early benefits were evident in the trial, with the survival advantage becoming clearer as the data matured.
J&J’s journey with this combination began with its 2018 partnership with Yuhan Corporation, which brought Lazcluze into its portfolio. Rybrevant, on the other hand, received its first FDA approval in 2021 for treating NSCLC patients with exon 20 insertion mutations. The combination therapy’s approval provides a much-needed alternative for patients, especially given that the five-year survival rate for those with advanced EGFR-mutated NSCLC remains under 20%. In the U.S., approximately 30,000 people are diagnosed with this condition annually.
Biljana Naumovic, J&J’s president of solid tumors, emphasized the benefits of the therapy for treatment-naïve patients, as it allows them to delay or avoid chemotherapy. “Rybrevant and Lazcluze is the only option that can give life to patients and actually reserves chemotherapy for the second line, where it belongs,” Naumovic said, contrasting it with AstraZeneca’s Tagrisso-chemo combination approved earlier in 2024.

Full results from the MARIPOSA trial are expected to be presented at upcoming conferences, providing more insights into the therapy’s impact. J&J also plans to discuss hyper-responders—patients achieving complete remission—who could represent a step closer to a potential cure.