FDA Approves Calquence for Mantle Cell Lymphoma

Calquence (acalabrutinib) was granted an accelerated approval by the FDA to treat adult patients with mantle cell lymphoma (MCL) following at least one prior therapy. The approval was based on objective response rates (ORR) in a single-arm trial.

The approval was based on findings from the 124-patient ACE-LY-004 phase 2 trial, in which the investigator assessed objective response rate (ORR) was 81 percent with Calquence. The complete response (CR) rate with acalabrutinib was 40 percent and the partial response (PR) rate was 41 percent.

In the 124-patient phase 2 trial, the ORR was 81 percent with Calquence, which was evenly split between complete responses (40 percent) and partial responses (41 percent). The approval for the novel BTK inhibitor 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, M.D., 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 Calquence at 100 mg twice daily. The median age of patients was 68 years, and most were male (80 percent). The median time since diagnosis was 46.3 months and 93 percent of patients had an ECOG performance status of 0 or 1. The median number of prior treatments was two (range, 1-5), which included stem cell transplant for 18 percent 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 percent, which was comprised evenly of CR and PR rates of 40 percent. The median duration of response was not yet reached at the time of analysis, with responses ongoing at 20-plus months. The median time to best response was 1.9 months.

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

The median duration of treatment with Calquence was 16.6 months (range, 0.1-26.6), with 73.4 percent of patients receiving the medication for six or more months and 59.7 percent on treatment for at least year. Overall, dose reductions due to AEs were required for 1.6 percent of patients and dose discontinuations were required for 6.5% of patients.

The phase 3 ACE-LY-308 clinical trial is currently evaluating Calquence in combination with bendamustine and Rituxan (rituximab) (BR) versus placebo plus BR for patients with untreated MCL.