FDA D.I.S.C.O. Burst Edition: Xalkori (crizotinib) and Darzalex Faspro (daratumumab plus hyaluronidase)
Welcome to the DISCO, FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide a quick update on two recent FDA cancer drug approvals.
On January 14, 2021, the FDA approved crizotinib (brand name Xalkori) for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma that is ALK-positive. The safety and efficacy of crizotinib have not been established in older adults with this type of lymphoma.
Efficacy was evaluated in a multicenter, single-arm, open-label trial in patients from 1 year up to 21 years of age that included 26 patients with relapsed or refractory, systemic ALK-positive ALCL after at least one systemic treatment. Efficacy was based on objective response rate and duration of response as assessed by an independent review committee. The objective response rate in the 26 patients was 88%, with a complete remission rate of 81%. Of the 23 patients who achieved a response, 39% maintained response for at least 6 months, and 22% maintained response for at least 12 months.
Ocular toxicity occurred in 65% of patients with ALCL, gastrointestinal toxicity occurred in 92%, and serious adverse reactions occurred in 35%, most often from neutropenia and infection. Due to the risk of visual loss, ophthalmologic evaluations are recommended at baseline and serially thereafter, coupled with monthly assessments of visual acuity and visual symptoms.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment and was approved approximately 6 weeks ahead of the FDA goal date.
On January 15, 2021, FDA granted accelerated approval to daratumumab plus hyaluronidase (brand name Darzalex Faspro) in combination with bortezomib, cyclophosphamide and dexamethasone for newly diagnosed light chain amyloidosis.
Efficacy was evaluated in an open-label, randomized, active-controlled trial in 388 patients with newly diagnosed light chain amyloidosis with measurable disease and at least one affected organ according to consensus criteria. Patients were randomized to receive bortezomib, cyclophosphamide, and dexamethasone, the control arm or with Darzalex Faspro in the investigational arm. The hematologic complete response rate based on established consensus response criteria as evaluated by an independent review committee was 42.1% for the investigational arm and 13.5% for the control arm.
The prescribing information includes a Warning and Precaution that serious or fatal cardiac adverse reactions occurred in patients with light chain amyloidosis who received Darzalex Faspro in combination with bortezomib, cyclophosphamide and dexamethasone. Darzalex Faspro is not indicated and is not recommended for the treatment of patients with light chain amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB disease outside of controlled clinical trials.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners.
The review also used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid which helped FDA approve this application 7 weeks ahead of the FDA goal date.
Full prescribing information for these approvals can be found on the web at www.fda.gov/