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Welcome back to the D.I.S.C.O., 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 19, 2023, the FDA granted accelerated approval to tucatinib (brand name Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Efficacy was evaluated in 84 patients in MOUNTAINEER, an open-label, multicenter trial. Patients were required to have HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer and prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-vascular endothelial growth factor monoclonal antibody. Patients whose tumors were deficient in mismatch repair proteins or were microsatellite instability-high must also have received an anti-programmed cell death protein-1 monoclonal antibody. Patients who received prior anti-HER2 targeting therapy were excluded.

The major efficacy measures were overall response rate and duration of response as assessed by blinded independent central review according to RECIST version 1.1. Overall response rate was 38% and median duration of response was 12.4 months.

The most common adverse events occurring in more than 20% of patients were diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. The most common laboratory abnormalities occurring in more than 20% were increased creatinine, increased glucose, increased ALT, decreased hemoglobin, increased AST, increased bilirubin, increased alkaline phosphatase, decreased lymphocytes, decreased albumin, decreased leukocytes, and decreased sodium.

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 application review is ongoing at the other regulatory agency.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

On January 19, 2023, the FDA also approved zanubrutinib (brand name Brukinsa) for chronic lymphocytic leukemia or small lymphocytic lymphoma.

Efficacy in patients with treatment-naïve chronic lymphocytic leukemia or small lymphocytic lymphoma was evaluated in SEQUOIA. In the randomized cohort including patients without 17p deletion, a total of 479 patients were randomized 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab for 6 cycles. The main efficacy outcome measure was progression-free survival as determined by an independent review committee. The median progression-free survival was not reached in the zanubrutinib arm and was 33.7 months in the bendamustine plus rituximab arm. Estimated median follow-up for progression-free survival was 25.0 months. In a separate non-randomized cohort of SEQUOIA, zanubrutinib was evaluated in 110 patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma with 17p deletion. Overall response rate per independent review committee was 88%. The median duration of response was not reached after a median follow-up of 25.1 months.

Efficacy in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma was evaluated in ALPINE. A total of 652 patients were randomized 1:1 to receive either zanubrutinib or ibrutinib. The median number of prior lines of therapy was 1 (ranging from 1 to 8). The main efficacy outcome measures at this time of response analysis were overall response rate and duration of response as determined by an independent review committee. The overall response rate was 80% in the zanubrutinib arm and 73% in the ibrutinib arm. The median duration of response was not reached in either arm, after a median follow-up of 14.1 months.

Across clinical trials of zanubrutinib, the most common adverse reactions occurring in more than 30% of patients were neutrophil count decreased, upper respiratory tract infection, platelet count decreased, hemorrhage, and musculoskeletal pain. Second primary malignancies, including non-skin carcinomas, developed in 13% of patients. Atrial fibrillation or flutter were reported in 3.7% of patients, and Grade 3 or higher ventricular arrhythmias in 0.2% of patients. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Full prescribing information for these approvals can be found on the web at www.fda.gov/drugsatFDA.

Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.

Follow the Division of Drug Information on Twitter @FDA_Drug_Info and the Oncology Center of Excellence @FDAOncology. Send your feedback via email to FDAOncology@fda.hhs.gov. Thanks for tuning in to the D.I.S.C.O Burst Edition.