The results from the Phase 3 MARIPOSA-2 study have been announced showing the regimen of amivantamab-vmjw given with or without lazertinib and combined with chemotherapy reduced the risk of disease progression or death by 56 and 52 percent respectively (Hazard Ratio [HR]=0.44; 95 percent Confidence Interval [CI], 0.35–0.56; p-value P<0.001 and HR=0.48; 95 percent CI, 0.36–0.64; P<0.001) compared to chemotherapy alone in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution, after disease progression on or after osimertinib.

Results also showed that the two amivantamab-vmjw regimens significantly improved objective response rate (ORR), intracranial progression-free survival (PFS), and duration of response (DOR) compared to chemotherapy alone in these patients. These data were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress taking place October 20-24, 2023 in Madrid, Spain (Abstract #LBA15) and simultaneously published in Annals of Oncology.

"The promising results from the MARIPOSA-2 study show that by combining amivantamab-vmjw with chemotherapy, both with and without lazertinib, patients achieved longer progression-free survival compared with chemotherapy alone," said Antonio Passaro,* M.D., Ph.D., medical oncologist of the Division of Thoracic Oncology, European Institute of Oncology in Milan, Italy, and presenting author. "The efficacy seen across the two amivantamab-vmjw regimens suggests that this treatment combination may address the diverse and often varied resistance that can occur in the post-osimertinib setting."

Amivantamab-vmjw plus chemotherapy reduced the risk of disease progression or death by 52 percent compared to chemotherapy alone (HR=0.48; 95 percent CI, 0.36–0.64; P<0.001). Amivantamab-vmjw plus chemotherapy with lazertinib reduced the risk of disease progression or death by 56 percent compared to chemotherapy alone (HR=0.44; 95 percent CI, 0.35–0.56; P<0.001). The improved PFS was consistent across all pre-specified patient subgroups, including age, sex, race, history of brain metastasis, smoking history, and lines of prior osimertinib therapy. Additionally, amivantamab-vmjw plus chemotherapy showed an ORR of 64 percent and amivantamab-vmjw plus chemotherapy and lazertinib demonstrated an ORR of 63 percent, compared to a response rate of 36 percent with chemotherapy alone.1

The data from MARIPOSA-2 are also the first to show that amivantamab-vmjw combination regimens may provide intracranial activity, which is critical for a disease where nearly 30 percent of patients develop brain metastases. Specifically, amivantamab-vmjw plus chemotherapy and amivantamab-vmjw plus chemotherapy and lazertinib reduced the risk of intracranial progression or death by 45 percent and 42 percent, respectively compared to chemotherapy alone (HR=0.55; 95 percent CI, 0.38–0.79; P=0.001 and HR=0.58; 95 percent CI, 0.44–0.78; P<0.001, respectively).

Early interim overall survival (OS) data show a trend favoring amivantamab-vmjw plus chemotherapy compared with chemotherapy alone (HR=0.77; 95 percent CI, 0.49–1.21). No difference in OS was observed at the interim analysis foramivantamab-vmjw plus chemotherapy and lazertinib compared with chemotherapy alone (HR=0.96; 95 percent CI, 0.67–1.35).

The safety profile for amivantamab-vmjw was consistent with prior reports. The most common adverse events (AEs) in the amivantamab-vmjw-containing arms were hAematologic, EGFR, and MET-related. Amivantamab-vmjw plus chemotherapy had lower rates of haematologic AEs than treatment with amivantamab-vmjw plus chemotherapy with lazertinib. The overall incidence of adverse events of special interest for the amivantamab-vmjw combination arms, including infusion-related reaction, rash, and pneumonitis, was comparable to that seen with amivantamab-vmjw monotherapy experience. Serious AEs occurred in 52 percent of patients receiving amivantamab-vmjw plus chemotherapy with lazertinib and 32 percent of patients treated with amivantamab-vmjw plus chemotherapy, compared with 20 percent of patients who received chemotherapy alone. The incidence of treatment-related AEs leading to death was low and comparable between all treatment arms. Rates of venous thromboembolism (VTE) were higher in the amivantamab-vmjw combinations, mostly Grade 1 or 2 with no Grade 5 events and rates of discontinuations due to VTEs were less than or equal to one percent. Incidence of interstitial lung disease (including pneumonitis) was three percent or less in all amivantamab-vmjw combinations.

"Amivantamab-vmjw plus chemotherapy, given with and without lazertinib, showed consistent disease control across all pre-specified patient subgroups in the MARIPOSA-2 study," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. "These encouraging results reinforce the distinct profile of amivantamab-vmjw-based regimens as potential practice-changing treatment options and mark another important key milestone in our pursuit to transform the treatment of EGFR-mutated NSCLC."

Amivantamab-vmjw is a bispecific antibody targeting EGFR and MET with immune cell-directing activity, and in the MARIPOSA-2 study was combined with chemotherapy (carboplatin and pemetrexed) and given with and without lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI) in patients with locally advanced or metastatic EGFR-mutated NSCLC after disease progression on or after osimertinib. In the study, 657 patients were randomised to receive treatment with amivantamab-vmjw and chemotherapy, either with or without lazertinib, or chemotherapy alone. Dual primary endpoints were used to compare PFS, as assessed by blinded independent central review (BICR), for each experimental arm to chemotherapy alone. Secondary endpoints included OS, ORR, DOR, and intracranial PFS.

Results from MARIPOSA-2 will support future planned health authority submissions.

Source: Janssen Pharmaceutical Companies of Johnson & Johnson