Johnson & Johnson's EGFR/c-MET Bispecific Antibody Combination Therapy Demonstrates Over One-Year Improvement in Overall Survival in Phase 3 MARIPOSA Trial

Jan 08, 2025 11:38 CST Updated 11:38

Johnson & Johnson

Medical Device R&D and Manufacturer

On January 7, Johnson & Johnson announcedMARIPOSA Phase 3 StudyPositive Top-Line Results for the Gold Standard Endpoint of Overall Survival (OS) in Cancer Treatment.

This study evaluated the efficacy of RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) as a first-line therapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) or L858R substitution mutations.

Data show that the chemo-free combination regimen achieved the final pre-specified secondary endpoint—OS, demonstrating a clinically meaningful and statistically significant improvement in OS compared to the current standard of care with osimertinib.The improvement in median OS is expected to exceed one year.

MARIPOSA is a randomized Phase 3 study,A total of 1,074 patients were enrolled. The combination of Rybrevant and Lazcluze was evaluated against active controls.Efficacy and Safety of Osimertinib Compared With. The primary endpoint of the study isAssessed by the Blinded Independent Central Review (BICR)Progression-Free Survival. Secondary endpoints include Overall Survival, Objective Response Rate (ORR), Duration of Response (DOR), Second Progression-Free Survival (PFS2), and Intracranial Progression-Free Survival.

Rybrevant and Lazcluze Combination TherapyThe overall safety profile is consistent with the safety profile of monotherapy.. In this combination therapy group, the incidence of adverse events was consistent with other Rybrevant treatment regimens, but observedVenous Thromboembolic EventsThe occurrence.Subsequent studies have shown that prophylactic administration of oral anticoagulants during the initial four months of the RYBREVANT® and LAZCLUZE™ regimen significantly reduces the risk of thrombosis.

The final overall survival analysis builds on the positive results of the previously reported interim analysis and progression-free survival analysis.These OS resultsTo be announced at an upcoming major medical conference and shared with global health organizations.

On October 17, 2023, with a median follow-up of 22 months, compared to osimertinib, the amivantamab-lazertinib groupSignificantly Reduce 30% PFS Risk(HR, 0.70; 95% CI, 0.58–0.85; P<0.001), mPFS reached 23.7 months (vs 16.6 months), ORR reached 86% (vs 85%), mDoR reached 25.8 months (vs 16.8 months), with greater PFS2 benefit (HR, 0.75; 95% CI, 0.58–0.98), and OS showing a trend toward benefit (HR, 0.80; 95% CI, 0.61 to 1.05; P=0.1).

InAt the WCLC 2024 conference, Johnson & Johnson presented longer follow-up data on overall survival (OS) for the EGFR-MET bispecific antibody Amivantamab in the Phase III MARIPOSA study (NCT04487080).

As of May 13, 2024 (median follow-up time, 31.1 months), 44% (185/421) and 34% (145/428) of patients in the Amivantamab + Lazertinib group and the Osimertinib group, respectively, were still on treatment. A total of 155 patients in the Amivantamab + Lazertinib group and 233 patients in the Osimertinib group experienced investigator-assessed disease progression and discontinued treatment, with 72% (111/155) and 74% (173/233) of patients starting subsequent therapy. The most common subsequent treatment regimens in the Amivantamab + Lazertinib group and the Osimertinib group were carboplatin-pemetrexed at 26% [29/111] and 28% [48/173], respectively. Progression-free survival after the first subsequent therapy (PFS2) favored Amivantamab + Lazertinib.（HR, 0.73; 95% CI, 0.59-0.91; nominal P=0.004）。Longer median time to discontinuation/next-line treatment, longer intracranial PFS,mOS was longer (NE vs 37.3, HR, 0.77; 95% CI, 0.61-0.96; nominal P=0.019).

Extended nearly 10 months of follow-up dataIndicates: 1.PFS2（HR=0.75→HR=0.73）and OS benefits (HR=0.80→HR=0.77) are all deeper and wider; 2.Amivantamab-lazertinib did not affect subsequent treatment; 3. The mOS of the osimertinib group was 37.3 months, consistent with 38.6 months in FLAURA, showing stable data.

Amivantamab is a bispecific antibody targeting EGFR and MET with immune cell-directing activity.Lazertinib is a third-generation EGFR TKI capable of penetrating the central nervous system.Based on the MARIPOSA Phase 3 study, RYBREVANT® in combination with LAZCLUZE™ has been approved in the United States and Europe for the first-line treatment of patients with epidermal growth factor receptor-mutated NSCLC.

Progression-Free Survival (PFS) tracks the length of time during which the patient's cancer does not progress due to treatment, whereas overall survival is different as it helps patients understand the impact of treatment on their lifespan from the start of treatment.Prolonging life expectancy is the most meaningful indicator to measure treatment effectiveness.

"Yusri Elsayed, M.D., Global Therapeutic Area Head of Oncology at Johnson & Johnson Innovative Medicine Companies, said: 'These new findings reinforce the clinical significance of this chemotherapy-free regimen for patients with non-small cell lung cancer worldwide and represent the first overall survival benefit compared to the current standard of care.' With less than 20% of patients surviving beyond five years, the needs of patients with epidermal growth factor receptor (EGFR) positive lung cancer remain unmet. The results from the MARIPOSA study indicate that RYBREVANT plus LAZCLUZE can extend patient survival beyond the current standard of care, providing patients with more time and hope in their fight against this devastating disease.""Extending the median overall survival by more than a year would be transformative for these patients."

Preliminary data from the MARIPOSA trial brings new optimism to the journey of extending life for patients with epidermal growth factor receptor mutations, adding another important option for patients and oncologists.

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