Janssen declares positive topline results from Phase 3 study evaluating RYBREVANT given with, without lazertinib combined with chemotherapy versus chemotherapy alone

New Jersey: The Janssen Pharmaceutical Companies of Johnson & Johnson has announced positive topline results from the three-arm Phase 3 MARIPOSA-2 study evaluating RYBREVANT (amivantamab-vmjw), a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), given with and without lazertinib, an oral, third-generation EGFR tyrosine kinase inhibitor (TKI), combined with chemotherapy (carboplatin and pemetrexed) versus chemotherapy alone.

MARIPOSA-2 enrolled patients with locally advanced or metastatic EGFR exon 19 deletions (ex19del) or L858R substitution NSCLC after disease progression on or after osimertinib. The study met its dual primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS versus chemotherapy alone in both experimental treatment arms. No new safety signals were found for the addition of RYBREVANT to chemotherapy.

Janssen plans to submit these results for presentation at upcoming scientific congresses, including details on secondary endpoints such as overall survival (OS), objective response, duration of response (DoR) and intracranial PFS.

“MARIPOSA-2 provides the first Phase 3 study data of RYBREVANT-based regimens in the broader EGFR-mutated non-small cell lung cancer population,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “The study builds on the significant innovation of RYBREVANT, a first-in-class bispecific antibody targeting two major oncogenic driver pathways, with clinically meaningful results that may change the treatment paradigm.”

MARIPOSA-2 (NCT04988295) is a randomized, open-label Phase 3 study evaluating the efficacy and safety of two regimens of RYBREVANT (with and without lazertinib) and chemotherapy. Patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after osimertinib were randomized to treatment with RYBREVANT plus chemotherapy, RYBREVANT plus chemotherapy with lazertinib, or chemotherapy alone. The dual primary endpoint was used to compare the PFS (using RECIST v1.1 guidelines*) as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone.

Secondary endpoints included objective response as assessed by BICR, OS, DoR, time to subsequent therapy, PFS after first subsequent therapy (PFS2) and intracranial PFS. All study participants underwent serial brain imaging to allow for the robust assessment of intracranial endpoints, and to assess the central nervous system (CNS) activity of RYBREVANT with and without lazertinib. As brain metastases can lead to significant burden and poor outcomes for patients, this aspect of the study design provides critical information in an area of high unmet need.

The study enrolled 657 patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after osimertinib. A RYBREVANT and lazertinib combination is also being evaluated in the first-line setting for patients with EGFR-mutated NSCLC in the pivotal Phase 3 MARIPOSA study. MARIPOSA is comparing the combination therapy of RYBREVANT and lazertinib head-to-head versus osimertinib, in addition to a third arm of lazertinib to assess the contribution of components.

Read also: Janssen seeks USFDA full approval for Balversa for Urothelial Carcinoma