FDA D.I.S.C.O. Burst Edition: FDA approvals of Tukysa (tucatinib) with trastuzumab for colorectal cancer and Brukinsa (zanubrutinib) for chronic lymphocytic leukemia or small lymphocytic lymphoma

Regulatory approval news: On Jan 19, 2023, the FDA granted accelerated approval to tucatinib (Tukysa) plus trastuzumab for RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer after progression on fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. The FDA also approved zanubrutinib (Brukinsa) for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), supported by SEQUOIA and ALPINE trial results.

FDA D.I.S.C.O. Burst Edition (Regulatory approvals) — Jan 19, 2023

Tucatinib (Tukysa) + trastuzumab in colorectal cancer (accelerated approval)

The FDA granted accelerated approval to tucatinib 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 MOUNTAINEER (open-label, multicenter; n=84). Major efficacy measures were overall response rate (ORR) and duration of response (DOR) by blinded independent central review (RECIST v1.1): ORR 38%; median DOR 12.4 months.

Common adverse events (>20%) included diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and pyrexia. Common lab abnormalities (>20%) included increased creatinine/glucose/ALT/AST/bilirubin/alkaline phosphatase, and decreased hemoglobin/lymphocytes/albumin/leukocytes/sodium.

The review was conducted under Project Orbis; review by another regulatory agency was described as ongoing.

Zanubrutinib (Brukinsa) in CLL/SLL

The FDA also approved zanubrutinib for CLL or SLL.

  • SEQUOIA (treatment-naïve, no del(17p)): n=479, zanubrutinib vs bendamustine+rituximab. Median PFS not reached vs 33.7 months; follow-up 25.0 months.
  • SEQUOIA (non-randomized del(17p) cohort): n=110, ORR 88%; median DOR not reached (follow-up 25.1 months).
  • ALPINE (relapsed/refractory): n=652, zanubrutinib vs ibrutinib; ORR 80% vs 73%; median DOR not reached (follow-up 14.1 months).

Across zanubrutinib trials, common adverse reactions (>30%) included neutrophil count decreased, upper respiratory tract infection, platelet count decreased, hemorrhage, and musculoskeletal pain; second primary malignancies occurred in 13%; atrial fibrillation/flutter in 3.7%; Grade ≥3 ventricular arrhythmias in 0.2%.

Prescribing information: www.fda.gov/drugsatFDA.

Sources