Phase 3 MARIPOSA-2 Study Shows RYBREVANT®▼(amivantamab) Plus Chemotherapy Given with or without Lazertinib Reduced Risk of Disease Progression or Death by 56 and 52 Percent Respectively in Patients with EGFRMutated Non-Small Cell Lung Cancer who Progressed on or after Osimertinib

Phase 3 MARIPOSA-2 Study Shows RYBREVANT®▼(amivantamab) Plus Chemotherapy Given with or without Lazertinib Reduced Risk of Disease Progression or Death by 56 and 52 Percent Respectively in Patients with EGFRMutated Non-Small Cell Lung Cancer who Progressed on or after Osimertinib

These amivantamab regimens are the first to show improvement in progression-free survival compared to chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) following prior osimertinib treatment1

Late-breaking results from MARIPOSA-2 study were presented in a Presidential Symposium at 2023 ESMO Congress and simultaneously published in Annals of Oncology1,2

BEERSE, BELGIUM, 23 October, 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 3 MARIPOSA-2 study showing the regimen of RYBREVANT®▼(amivantamab) 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<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.1 Results also showed that the two amivantamab regimens significantly improved objective response rate (ORR), intracranial progression-free survival (icPFS), and duration of response (DOR) compared to chemotherapy alone in these patients.1 These data were presented in a Presidential Symposium at the European Society for Medical CP-417580 October 2023 Oncology (ESMO) 2023 Congress taking place 20-24 October in Madrid, Spain (Abstract #LBA15) and simultaneously published in Annals of Oncology. 1,2

“The promising results from the MARIPOSA-2 study show that by combining amivantamab with chemotherapy, both with and without lazertinib, patients achieved longer progressionfree 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 regimens suggests that this treatment combination may address the diverse and often varied resistance that can occur in the post-osimertinib setting.”

Amivantamab plus chemotherapy reduced the risk of disease progression or death by 52 percent compared to chemotherapy alone, with a median PFS of 6.3 versus 4.2 months (HR=0.48; 95 percent CI, 0.36–0.64; P<0.001).1 Amivantamab plus chemotherapy with lazertinib reduced the risk of disease progression or death by 56 percent compared to chemotherapy alone, with a median PFS of 8.3 versus 4.2 months (HR=0.44; 95 percent CI, 0.35–0.56; P<0.001).1 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.1 Additionally, amivantamab plus chemotherapy showed an ORR of 64 percent and amivantamab plus chemotherapy with 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 combination regimens may provide intracranial activity, which is critical for a disease where nearly 30 percent of patients develop brain metastases.1,3 Specifically, amivantamab plus chemotherapy reduced the risk of intracranial progression or death by 45 percent compared to chemotherapy alone, with a median icPFS of 12.5 versus 8.3 months (HR=0.55; 95 percent CI, 0.38–0.79; P=0.001).1

Amivantamab plus chemotherapy and lazertinib also reduced the risk of intracranial progression or death, by 42 percent, compared to chemotherapy alone, with a median icPFS of 12.8 versus 8.3 months (HR=0.58; 95 percent CI, 0.44–0.78; P<0.001).1

“EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations in NSCLC, and patients with these mutations are faced with a five-year overall survival rate of only 19 percent,” said Martin Vogel, EMEA Therapeutic Area Lead Oncology, Jannsen-Cilag GmbH.

“These amivantamab-based regimens are the first to show improved progression-free survival in this patient population after disease progression on osimertinib and provide new hope for patients who have limited options remaining.”

Early interim overall survival (OS) data showed a trend favouring amivantamab 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 for amivantamab plus chemotherapy and lazertinib compared with chemotherapy alone (HR=0.96; 95 percent CI, 0.67–1.35).1

The safety profile for amivantamab was consistent with prior reports. The most common adverse events (AEs) in the amivantamab-containing arms were haematologic, EGFR, and MET-related.1 Amivantamab plus chemotherapy had lower rates of haematologic AEs than treatment with amivantamab plus chemotherapy with lazertinib.1 The overall incidence of AEs of special interest for the amivantamab combination arms, including infusion-related reaction, rash and pneumonitis, was comparable to that seen with amivantamab monotherapy experience.1 Serious AEs occurred in 52 percent of patients receiving amivantamab plus chemotherapy with lazertinib and 32 percent of patients treated with amivantamab plus chemotherapy, compared with 20 percent of patients who received chemotherapy alone.1 The incidence of treatment-related AEs leading to death was low and comparable between all treatment arms.1 Rates of venous thromboembolism (VTE) were higher in the amivantamabcombinations, 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-combinations.1

“Amivantamab 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-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 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 CP-417580 October 2023 kinase inhibitor (TKI) in patients with locally advanced or metastatic EGFR-mutated NSCLC after disease progression on or after osimertinib.1,4,5,6,7,8 In the study, 657 patients were randomised to receive treatment with amivantamab and chemotherapy, either with or without lazertinib, or chemotherapy alone.1 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.1

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