- U.S. Food and Drug Administration (FDA) (https://voice.ons.org/topic/us-food-and-drug-administration-fda)
- Lung Cancer (https://voice.ons.org/topic/lung-cancer)
- Clinical practice (https://voice.ons.org/topic/clinical-practice)
- Oncology drug research (https://voice.ons.org/topic/oncology-drug-research)
FDA Grants Accelerated Approval to Amivantamab-Vmjw for Metastatic NSCLC
On May 21, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-amivantamab-vmjw-metastatic-non-small-cell-lung-cancer) to amivantamab-vmjw (Rybrevant™), a bispecific antibody directed against epidermal growth factor receptor (EGFR) and MET receptor, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. FDA also approved the Guardant360® CDx as a companion diagnostic.
“Advancements in precision oncology continue to facilitate drug development, allowing diseases like lung cancer to be subset into biomarker-defined populations appropriate for targeted therapies,” Julia Beaver, MD, chief of medical oncology at FDA’s Oncology Center of Excellence and acting deputy director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research, said. “With today’s approval, for the first time, patients with NSCLC with EGFR exon 20 insertion mutations will have a targeted treatment option.”
Approval was based on a multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS; NCT02609776) of patients with locally advanced or metastatic NSCLC. Efficacy was evaluated in 81 patients with advanced NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. Patients received amivantamab-vmjw once weekly for four weeks then every two weeks thereafter until they experienced disease progression or unacceptable toxicity.
The main efficacy outcome measurements were overall response rate (ORR) according to response evaluation criteria for solid tumors 1.1 as evaluated by blinded independent central review and response duration. ORR was 40% (95% CI = 29%, 51%) with a median response duration of 11.1 months (95% CI = 6.9, not evaluable).
The most common adverse reactions (≥ 20%) were rash, infusion-related events, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. Amivantamab-vmjw should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if i confirmed. Patients taking amivantamab-vmjw should limit sun exposure during and for two months after treatment. Amivantamab-vmjw may cause problems with vision. Because it may cause fetal harm, verify the pregnancy status of patients of reproductive potential before starting treatment.
The recommended dose of amivantamab-vmjw is 1,050 mg for patients with baseline body weight less than 80 kg and 1,400 mg for body weights of 80 kg or more, administered weekly for four weeks, then every two weeks until patients experience disease progression or unacceptable toxicity.
FDA gave the indication accelerated approval based on ORR and duration of response. Continued approval for the indication is contingent on verification and description of clinical benefit in confirmatory trials.
FDA conducted the review under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Brazilian Health Regulatory Agency and the United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
The review used Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application two months ahead of its goal date.
The product was granted breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov)