General Information

Rybrevant (amivantamab-vmjw) is a bispecific EGF receptor-directed and MET receptor-directed antibody.

Rybrevant is specifically indicated for use in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

Rybrevant is supplied as a solution for intravenous administration. The recommended doses of Rybrevant are based on baseline body weight.

• Body Weight at Baseline: Less than 80 kg
  • Recommended Dose: 1050 mg
  • Number of 350 mg/7 mL Rybrevant Vials: 3

• Body Weight at Baseline: Greater than or equal to 80 kg
  • Recommended Dose: 1400 mg
  • Number of 350 mg/7 mL Rybrevant Vials: 4

Administer Rybrevant weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks thereafter until disease progression or unacceptable toxicity. Administer premedications before each Rybrevant infusion as recommended. Please see the drug label for the diluted Rybrevant infusion rates. 

Mechanism of Action

Rybrevant (amivantamab-vmjw) is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab-vmjw was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively.

Side Effects

Adverse effects associated with the use of Rybrevant may include, but are not limited to, the following:

• rash
• IRR
• paronychia
• musculoskeletal pain
• dyspnea
• nausea
• fatigue
• edema
• stomatitis
• cough
• constipation
• vomiting
• Grade 3 or 4 laboratory abnormalities: decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium

Clinical Trial Results

Rybrevant for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

CHRYSALIS is a Phase 1 open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of Rybrevant as a monotherapy and in combinations including with lazertinib, a novel third-generation EGFR TKI16, in adults with advanced NSCLC. The study consists of two parts: Rybrevant monotherapy and combination-dose escalations and Rybrevant monotherapy and combination-dose expansions. 

In the ongoing Phase 1 CHRYSALIS study, patients with locally advanced or metastatic NSCLC with EGFR Exon 20 insertion mutations weighing less than 80 kg received Rybrevant 1050 mg and patients weighing at least 80 kg or more received Rybrevant 1400 mg weekly for four weeks, with the initial dose as a split infusion in week 1 on day 1 and day 2,  then administered every two weeks thereafter until disease progression or unacceptable toxicity.1 Disease response using overall response rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1) as evaluated by Blinded Independent Central Review (BICR), was the primary endpoint. In the prior-platinum chemotherapy treated cohort (n=81), the confirmed ORR, as assessed by blinded independent central review, was 40 percent, with 3.7 percent having complete responses (CR) and 36 percent achieving partial responses (PR).