The Janssen Pharmaceutical Companies of Johnson & Johnson today announced positive topline results from the Phase 3 MARIPOSA study evaluating RYBREVANT® (amivantamab-vmjw), a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), in combination with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), versus osimertinib as first-line treatment in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC)....The pivotal Phase 3 MARIPOSA study met its primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients receiving RYBREVANT® plus lazertinib compared to osimertinib.

...Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous NSCLC, characterized at or after the time of locally advanced metastatic disease diagnosis by either EGFR Exon 19del or Exon 21 L858R mutation, by an FDA-approved or other validated test of either ctDNA or tumor tissue in a CLIA certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US). ...

...Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with previously epidermal growth factor receptor (EGFR) mutation (identified locally in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory [or equivalent]) that is metastatic or unresectable, and have progressed after standard of care front-line therapy, and exhausted available options with targeted therapy....

...- Mandatory submission of unstained tissue from tumor (in a quantity sufficient to allow for central analysis of EGFR mutation status and blood (for circulating tumor deoxyribonucleic acid [ctDNA], digital droplet polymerase chain reaction [ddPCR], and pharmacogenomic analysis)...

...- Somatic activating mutation in EGFR in a prior tumor biopsy or cfDNA sample...

...A copy of the test report documenting the EGFR mutation must be included in the participant records and must also be submitted to the sponsor prior to enrollment; 4....

...- Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation...

Patients received intravenous amivantamab 1400 mg (1750 mg, ≥80 kg) weekly for the first 4 weeks and 1750 mg (2100 mg, ≥80 kg) every 3 weeks starting at cycle 3 plus 240 mg oral lazertinib daily, and pemetrexed (500 mg/m2) with carboplatin (AUC5 for the first 4 cycles) on a 21-day cycle....Among patients with EGFR-mutated advanced NSCLC who experienced disease progression on EGFR TKIs, amivantamab, lazertinib plus chemotherapy demonstrated meaningful and durable response rates.

CHRYSALIS-2 (NCT04077463) is an ongoing open-label study with an expansion cohort (C) examining amivantamab + lazertinib in advanced NSCLC with atypical non-exon 20 insertion EGFR mutations...A best response of partial response (PR) was observed in 60.0% (24/40).... Of the 30 patients who had ≥3 scheduled post baseline assessments or discontinued for any reason, the objective response rate was 56.7%, with 16 (53.3%) achieving a confirmed PR...Among a patient population with few treatment options, amivantamab combined with lazertinib demonstrated encouraging anti-tumor activity in a majority of patients with a tolerable safety profile.

Amivantamab in combination with lazertinib and chemotherapy yielded high overall response rates in patients who progressed on EGFR TKIs as prior line of therapy. The safety profile of the LACP regimen was consistent with the individual agents, with no evidence of new safety signals or additive toxicity.

As of 19 Apr 2021, 121 pts in the mono group (85% with EGFR/MET-based resistance) and 45 in the combo group (38% with EGFR/MET-based resistance) were efficacy-evaluable...Antitumor activity was observed in the mono group, with 33 achieving partial response (PR) as best response, of which 23 were confirmed, for an overall response rate (ORR) of 19% (95% CI, 12–27). In the combo group, 1 complete response and 15 PRs were observed, all of which confirmed, for an ORR of 36% (95% CI, 22–51).