Johnson & Johnson has redrawn the survival map in EGFR-mutant lung cancer.
At the European Lung Cancer Congress (ELCC) 2025, the company unveiled overall survival data from its phase 3 MARIPOSA trial, showing its chemotherapy-free combination of Rybrevant (amivantamab) and Yuhan’s Lazcluze (lazertinib, branded as Leclaza in Korea) cut the risk of death by 25 percent compared to AstraZeneca's Tagrisso (osimertinib) in previously untreated advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.
The J&J combo hasn’t yet reached median overall survival (OS), but its survival curve outpaced Tagrisso’s 36.7 months and kept widening over time—leading investigators to expect at least a one-year survival advantage, according to the company.
J&J’s chemo-free lung cancer combo may extend survival by at least a year compared to Tagrisso. (Credit: Getty Images)
J&J’s chemo-free lung cancer combo may extend survival by at least a year compared to Tagrisso. (Credit: Getty Images)
At three years, 60 percent of patients on the combination were alive, compared with 51 percent on Tagrisso. At 42 months, survival rates were 56 percent versus 44 percent.
Before MARIPOSA, “you have a one in two chance of being alive at three years” was the typical script oncologists gave patients, said Mark Wildgust, J&J’s VP of global medical affairs, during an expert panel at ELCC. But, he added, “now you have a one in two chance of being alive at four years.”
Looking at the tail of the curve, he suggested the field may soon be “thinking about resetting that five year survival rate as well.”
According to J&J data, the survival advantage began around month 10 and continued to widen. Wildgust said the flattening tail resembled what’s often seen with immunotherapy—and credited the combo’s triple mechanism for delaying resistance, including MET amplification and small-cell transformation.
Lazertinib is a third-generation EGFR inhibitor that targets the same mutation as Tagrisso. Rybrevant, a bispecific antibody, blocks both EGFR and MET, an EGFR escape pathway—while also engaging immune cells through its engineered Fc domain.
Enriqueta Felip, section chief of oncology at Vall d'Hebron University Hospital and MARIPOSA’s presenting investigator, said the data support J&J’s long view. “Seeing how the curves are evolving—yes, we can expect that this could be a reality at five years,” she said.
The combo also held its ground in the brain—long considered a therapeutic weak spot. At three years, intracranial progression-free survival hit 36 percent on the combo, doubling the 18 percent seen with Tagrisso.
Median intracranial response duration stretched to 35.7 months, compared to 29.6. Meanwhile, the time to symptomatic progression—when patients begin to feel their disease worsen—was delayed by more than 14 months.
Toxicity remains the trade-off. Grade 3 or higher rash occurred in 17 percent of patients, compared to 1 percent on Tagrisso. Paronychia hit 12 percent of combo patients, versus less than 1 percent with Tagrisso. Venous thromboembolism reached 40 percent versus 11 percent.
But J&J shared bar graph data showing most of the adverse events clustered in the first four months and declined after that.
"We can say—and this is very important—that first-line amivantamab plus lazertinib led to a statistically significant and clinically meaningful reduction in mortality versus osimertinib," Felip said, citing a hazard ratio of 0.75.
Despite tolerability trade-offs, second-line access remained intact. Seventy-four percent of patients in the combo group proceeded to next-line therapies, closely matching the 76 percent rate seen in the Tagrisso arm.
tweet
Related articles
Oscotec faces investor backlash over Genesco IPO as CEO warns of R&D shutdown
Will Leclaza-Rybrevant combo therapy open new horizon for EGFR lung cancer treatment?
Yuhan's 2024 revenue surpasses ₩2 trillion thanks to lung cancer drug
SC formulation of Rybrevant-Leclaza combo therapy endorsed for approval in Europe
[JPM2025] J&J says Leclaza combo therapy’s potential is undervalued – and for good reason
Yuhan’s lung cancer drug lazertinib gets nod in Europe
[Top 10 Healthcare News in 2024 ⑦] Yuhan’s Leclaza makes US entry to become a global blockbuster
Yuhan milestone payments 'unaffected' by FDA CRL of J&J’s subcutaneous Rybrevant
Kim Ji-hye jkim404@docdocdoc.co.kr
See Other Articles
Copyright © KBR Unauthorized reproduction, redistribution prohibited