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2021 antibody new drug: Amivantamab-vmjw and its Adverse reactions
2021 antibody new drug: Amivantamab-vmjw and its Adverse reactions. This article provides the reviews of Amivantamab-vmjw.
On May 21, 2021, the U.S. Food and Drug Administration (FDA) approved amivantamab-vmjw (trade name RYBREVANT) for the first time for the treatment of disease progression and epidermal growth factor receptor (EGFR) during or after platinum-containing chemotherapy. Patients with metastatic non-small cell lung cancer (NSCLC) with insertion mutation in exon 20 of the gene.
Amivantamab is a bispecific antibody that simultaneously targets EGFR and cMET. It can not only block the binding of ligands to EGFR and MET, promote receptor degradation, but also trigger antibody-dependent cellular cytotoxicity.
It is worth mentioning that amivantamab is the first targeted therapy approved by the FDA for the treatment of EGFR exon 20 insertion mutations. This approval is based on the positive results of the Phase I CHRYSALIS study (NCT02609776).
The recommended dose of amivantamab is based on baseline body weight. It is given once a week for the first 4 weeks, the first dose is given over 2 days, and the dose is maintained every 2 weeks after 4 weeks.
amivantamab is developed by Johnson & Johnson’s Janssen Pharmaceuticals. The production and development of amivantamab uses Genmab’s DuoBody technology platform.
Pharmacodynamics and pharmacokinetics
Amivantamab is a bispecific antibody that can simultaneously bind to the extracellular domain of EGFR and MET. In in vitro and in vivo studies, amivantamab can disrupt EGFR and MET signaling functions by blocking ligand binding and degrading EGFR and MET in the exon 20 insertion mutation model.
The presence of EGFR and MET on the surface of tumor cells also makes immune effector cells. (Such as natural killer cells and macrophages) target tumor cells to kill through antibody-dependent cytotoxicity (ADCC) and phagocytic mechanisms, respectively.
Within the dose range of 350-1750 mg (0.25-1.25 times the maximum approved recommended dose), Amivantamab exposure increased proportionally. At the 9th infusion, the concentration of Amivantamab reached a steady state. The cumulative ratio at steady state is 2.4. The mean volume of distribution (± SD) of amivantamab is 5.13 (±1.78) liters. The average elimination rate was 360 (±144) mL/day, and the terminal half-life was 11.3 (±4.53) days.
CHRYSALIS is a multi-center, open-label, multi-cohort phase I clinical trial that evaluates amivantamab in patients with locally advanced or metastatic non-small cell lung cancer. Patients enrolled in this study included patients with locally advanced or metastatic non-small cell lung cancer whose EGFR exon 20 insertion mutation progressed during or after platinum-based chemotherapy. Patients with untreated brain metastases and patients with a history of ILD who needed long-term use of steroids or other immunosuppressive agents in the past 2 years were excluded from this study.
Patients received amivantamab 1050 mg (baseline weight <80 kg) or 1400 mg (baseline weight ≥80 kg) once a week for 4 weeks and then every 2 weeks until the disease progressed or unacceptable toxicity appeared. The main efficacy indicators are the total effective rate (ORR) and duration of response (DOR), clinical benefit rate, and progression-free survival (PFS) through blinded independent center evaluation (BICR) based on the efficacy evaluation criteria for solid tumors (recistv1.1) And overall survival (OS).
The results showed that in the post-platinum curative effect cohort (n=81), the ORR was 40% (n=32, 95%CI: 29-51), of which 3 cases (4%) achieved complete remission (CR) and 29 cases ( 36%) achieved partial remission (PR). Among patients who achieved remission, the remission performance was long-lasting, with a median DOR of 11.1 months (95%CI: 6.9-not reached [NE]). Among them, 20 patients (63%) had remission lasting ≥6 months. The median PFS was 8.3 months (95%CI: 6.5–10.9), and the median OS was 22.8 months (95%CI: 14.6-not reached [NE]). The clinical benefit rate (≥PR or stable disease≥11 weeks) was 74% (95%CI: 63-83).
Among patients treated with RP2D dose amivantamab (n=114), the most common adverse events (TEAE) during treatment were skin rash (86%), infusion-related reactions (IRR, 66%), paronychia (45%) ). Other adverse events were stomatitis (21%) and itching (17%). 35% of patients reported ≥ grade 3 adverse events, of which 16% were considered treatment-related, the most common being rash (4%) and IRR (3%). No deaths related to treatment were reported. Treatment-related adverse events leading to dose reduction and discontinuation were 13% and 4%, respectively.
Like all therapeutic proteins, amivantamab is immunogenic. In the CHRYSALIS study, among 286 patients who took amivantamab at the recommended therapeutic dose, 1% (3/286) of the patients had detected anti-antibodies (ADAs) against amivantamab.
(source:internet, reference only)