On September 19, 2024, the Food and Drug Administration sanctioned amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) in conjunction with carboplatin and pemetrexed for adult patients diagnosed with locally advanced or metastatic non-small cell lung cancer (NSCLC) exhibiting epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, whose condition has advanced following treatment with an EGFR tyrosine kinase inhibitor.
Effectiveness and Safety
The efficacy was assessed in MARIPOSA-2 (NCT04988295), a randomized, open-label, multicenter trial involving 657 patients with locally advanced or metastatic NSCLC exhibiting EGFR exon 19 deletions or exon 21 L858R substitution mutations, who had tumor progression following treatment with osimertinib. Patients were randomized in a 1:2:2 ratio to receive amivantamab-vmjw in conjunction with carboplatin and pemetrexed (amivantamab + CP), carboplatin and pemetrexed (CP) alone, or amivantamab-vmjw as part of an alternative combination regimen.
The primary efficacy outcome measure was progression-free survival (PFS) evaluated by blinded independent central review (BICR) for the comparison of amivantamab + CP with CP. The overall response rate (ORR) as assessed by BICR and overall survival (OS) were major secondary outcome measures. The median progression-free survival (PFS) was 6.3 months (95% confidence interval: 5.6, 8.4) in the amivantamab plus chemotherapy (CP) group and 4.2 months (95% confidence interval: 4.0, 4.4) in the chemotherapy group (hazard ratio 0.48 [95% confidence interval: 0.36, 0.64], p-value < 0.0001). The confirmed overall response rate (ORR) was 53% (95% confidence interval: 44, 62) in the amivantamab plus chemotherapy arm and 29% (95% confidence interval: 23, 35) in the chemotherapy arm (p-value < 0.0001).
At the predetermined second intermediate analysis of overall survival (OS), with 85% of the requisite deaths for the final analysis, no statistically significant difference in OS was observed. The stratified overall survival hazard ratio was 0.73 (95% confidence interval: 0.54, 0.99).
The predominant adverse responses (≥20%) included rash, infusion-related symptoms, exhaustion, nail toxicity, nausea, constipation, edema, stomatitis, diminished appetite, musculoskeletal discomfort, vomiting, and COVID-19 infection.
The prescribed dosage of amivantamab-vmjw is determined by initial body weight. Refer to the prescription instructions for detailed dose guidelines.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
