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Acalabrutinib Granted Accelerated Approval from FDA for MCL

Silas Inman
Published Online:4:52 PM, Tue October 31, 2017
Acalabrutinib (Calquence) received an accelerated approval from the FDA for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least 1 prior regimen.

The accelerated approval was based on findings from the 124-patient ACE-LY-004 phase II trial, in which the investigator assessed objective response rate (ORR) was 81% with acalabrutinib (95% CI, 73%-87%). The complete response (CR) rate with acalabrutinib was 40% and the partial response (PR) rate was 41%.

The approval for the novel BTK inhibitor acalabrutinib arrived several months ahead of expectations under the Prescription Drug User Fee Act and followed a breakthrough therapy designation from the FDA for MCL in early August.

“Mantle cell lymphoma is a particularly aggressive cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “For patients who have not responded to treatment or have relapsed, Calquence provides a new treatment option that has shown high rates of response for some patients in initial studies.”

In the ACE-LY-004 study, 124 patients with MCL received oral acalabrutinib at 100 mg twice daily. The median age of patients was 68 years, and most were male (80%). The median time since diagnosis was 46.3 months and 93% of patients had an ECOG performance status of 0 or 1. The median number of prior treatments was 2 (range, 1-5), which included stem cell transplant for 18% of patients. Those treated with a prior BTK inhibitor were excluded from the trial.

At a median follow-up of 15.2 months, the ORR by independent review committee was 80% (95% CI, 72%-87%), which was comprised evenly of CR and PR rates of 40%. The median duration of response was not yet reached at the time of analysis, with responses ongoing at 20+ months. The median time to best response was 1.9 months.

The most common adverse events (AEs) of any grade were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%), which is a known class effect for BTK inhibition. Most bruising events were grade 1 in severity (19%). The most common grade ≥3 AEs were neutropenia (15%), thrombocytopenia (12%), anemia (10%), and diarrhea (3.2%).

The median duration of treatment with acalabrutinib was 16.6 months (range, 0.1-26.6), with 73.4% of patients receiving the medication for ≥6 months and 59.7% of patients on treatment for ≥1 year. Overall, dose reductions due to AEs were required for 1.6% of patients and dose discontinuations were required for 6.5%.

Under the accelerated approval program, full approval for acalabrutinib is contingent on findings from confirmatory trials. Currently, the phase III ACE-LY-308 clinical trial is evaluating acalabrutinib in combination with bendamustine and rituximab (BR) versus placebo plus BR for patients with untreated MCL.

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