Lazertinib

iStock, BrasilNut1 The latest data from Johnson and Johnson’s Rybrevant and Lazcluze lung cancer combo was better than standard of care Tagrisso on overall survival. But analysts say the next step is getting a subcutaneous formula approved. A combo regimen of Johnson & Johnson ’s Rybrevant and Lazcluze significantly prolonged overall survival in non-small cell lung cancer patients, beating AstraZeneca’s Tagrisso in a late-stage trial. “We view today’s update as an incremental positive for JNJ,” analysts at Guggenheim Partners wrote in a note on Wednesday evening, adding that the findings are “in line” with a September 2024 readout . At the time, J&J reported a 23% overall survival benefit in patients on Rybrevant plus Lazcluze. Though data were still immature for statistical analysis, the pharma had called the OS trend “strong and improving.” J&J updated these results in the latest release from the Phase III MARIPOSA study on Wednesday. At a median follow-up of 37.8 months, Rybrevant plus Lazcluze lowered the risk of death from any cause by 25% as compared with Tagrisso. This effect was highly statistically significant, according to J&J. MARIPOSA tested the Rybrevant regimen as a first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring specific EGFR mutations. At the time of the readout, median OS had not yet been reached in patients treated with Rybrevant and Lazcluze, “indicating that survival benefits continue to extend beyond the measured follow-up period,” according to J&J. Median OS in Tagrisso comparators was 36.7 months. J&J also conducted survival projections for study participants treated with the drug combo and found that Rybrevant plus Lazcluze could likely extend median OS by at least 12 months versus Tagrisso. MARIPOSA also met multiple secondary endpoints, demonstrating that the Rybrevant combo was superior to Tagrisso in terms of intracranial progression-free survival, intracranial duration of response and intracranial overall response rate. J&J’s regimen also significantly delayed symptom progression. The combo of Rybrevant and Lazcluze has been approved since August 2024, when the FDA hgave the green light for the regimen to be used as a first-line option in a subgroup of patients with EGFR mutations and with locally advanced or metastatic disease. Tagrisso is currently a common treatment option in this indication. J&J on Wednesday said that it plans on sharing the updated OS data from MARIPOSA with health regulators worldwide. According to the Guggenheim analysts, however, “the next key step” for the Rybrevant-Lazcluze combo “would be obtaining FDA approval” for a subcutaneous formulation of Rybrevant. In December 2024, the regulator rebuffed J&J’s first attempt at this, citing concerns with a manufacturer. The regulator did not identify problems with the drug formulation or with its data package. If approved, subcutaneous Rybrevant could “offer patients a more tolerable option as the company works towards its goal of >$5bn in annual peak sales for the franchise,” according to the Guggenheim analysts.

Johnson & Johnson (J&J) has announced that its chemotherapy-free combination significantly extended overall survival (OS) compared to standard of care in a subset of non-small cell lung cancer (NSCLC) patients. The phase 3 MARIPOSA study has been evaluating Rybrevant (amivantamab), an EGFR-MET bispecific antibody, plus Lazcluze (lazertinib), a third-generation EGFR tyrosine kinase inhibitor (TKI), against AstraZeneca’s own third-generation EGFR-TKI Tagrisso (osimertinib) as a first-line treatment for locally advanced or metastatic NSCLC in patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations. J&J previously reported in 2023 that the study met its primary endpoint, with the combination demonstrating a statistically significant and clinically meaningful improvement in progression-free (PFS) compared to Tagrisso. New data presented at this year’s European Lung Cancer Congress showed that, at a median follow-up of 37.8 months, median OS for Rybrevant plus Lazcluze had not yet been reached, while median OS for Tagrisso-treated patients was 36.7 months. Among patients receiving J&J’s combination, 56% were alive at three and a half years compared to 44% of patients on Tagrisso, with projections suggesting Rybrevant plus Lazcluze could extend median OS by at least 12 months compared to AZ’s drug. The combination also prolonged multiple secondary endpoints versus Tagrisso, including intracranial PFSl, intracranial duration of response and intracranial overall response rate. NSCLC accounts for up to 85% of all lung cancer cases, and alterations in EGFR are among the most common driver mutations in patients with this form of the disease. “Right now, only 20% of patients with EGFR-positive NSCLC survive beyond five years,” explained Joshua Bauml, vice president, Lung Cancer Disease Area Stronghold Leader, J&J Innovative Medicine. “These MARIPOSA results suggest that Rybrevant plus Lazcluze can change this dire statistic that has been stagnant for far too long.” “This regimen isn’t just extending survival, it’s offering hope. By using Rybrevant plus Lazcluze first, we’re delaying the need for chemotherapy and giving patients and their families more time,” Bauml added. The announcement comes just three weeks after Lazcluze plus Rybrevant was approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for EGFR-mutated NSCLC. The combination has also already been approved in the US, EU and other markets for this indication. J&J said the latest OS results will be shared with health authorities globally.