FDA Fast Tracks Drug to Treat MCL

ICP-022 (orelabrutinib) has been granted a breakthrough therapy designation by the Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL).

A breakthrough therapy designation is given to speed up the development and FDA review of drugs that treat serious illnesses.

The new drug was designed to target B-cell lymphomas and autoimmune indications. The agent was developed to better be able to target certain cancer proteins than Imbruvica (ibrutinib) (Imbruvica) and Calquence (acalabrutinib), which should result in improved safety.

With a proprietary formulation, the agent is more readily used by the body than other BTK inhibitors.

“We are very proud that orelabrutinib was granted breakthrough therapy designation after obtaining orphan drug designation,” Jasmine Cui, cofounder, chairwoman, and chief executive officer of InnoCare Pharma, stated in a press release. “We will continue to uphold the concept of ‘science drives innovation for the benefit of patients’ and accelerate clinical trials for multiple indications of orelabrutinib in China and the rest of the world to benefit patients worldwide.”

In an open-label, multicenter, phase 2 trial, investigators set out to examine the safety, tolerability and efficacy of ICP-022, following oral administration, in Chinese patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small cell leukemia (SLL). The primary end point of the study was objective response rate (ORR), which is the percentage of patients whose cancer responded to the drug. Key secondary end points comprised duration of response (DOR; how long the response lasted), progression-free survival (PFS; the length of time patients survived on the drug without having their disease get worse) and safety. Response was evaluated in accordance with 2008 International Workshop on Chronic Lymphocytic Leukemia criteria with modification for partial response (PR) with lymphocytosis (PR-L).

The study was comprised of two stages. In the first stage, investigators evaluated the safety and tolerability of the BTK inhibitor given orally at a dose of 150 mg in patients with relapsed/refractory CLL/SLL. In the second stage of the research, which involved 80 patients, investigators examined the clinical benefits of ICP-022, when given at the same dose.

Eighty patients with relapsed/refractory CLL were enrolled to the trial; of these patients, 70 had CLL and 10 patients had SLL. At a data cutoff of May 31, 2019, half of patients (40) completed six cycles of treatment.

At an average follow-up of 6.3 months, 78 patients were determined to be evaluable for response. Results indicated that ICP-022 elicited an ORR of 88.5%, because 69 patients responded to the drug. One patient achieved a complete response, 39 experienced a partial response, and 29 reporting a PR-L. Moreover, 7.7% of patients experienced disease stability. The median DOR had not yet been reached, and the six-month DOR rate was 89.8%. The disease control rate achieved with the BTK inhibitor was 96.2%.

No significant differences in benefit were observed with ICP-022 across different subgroups analyzed, including age, disease stage, prior treatment, 17p deletion, 11q deletion, and IGHV mutation.

The most common side effects of any cause reported with the BTK inhibitor were hematologic toxicities that were well characterized; these effects included thrombocytopenia (low platelets), neutropenia (low neutrophils) and anemia (low red blood cell count). Patients also reported respiratory system infections and purpura (a rash caused by leaking blood vessels).

Notably, no patients experienced atrial fibrillation or secondary malignancy. The most common any-grade grade 3 or higher side effects comprised neutropenia, thrombocytopenia and lung infections.

A total of 25 patients reported at least one serious toxicity with the BTK inhibitor; 13 of these effects were determined to be associated with the agent and included decreased platelet count (three patients), pneumonitis (two patients), pyrexia (two patients) and herpes zoster (one patient).

In December 2020, China’s National Medical Products Administration (NMPA) approved the agent for use in the following indications: patients with relapsed/refractory CLL/SLL and those with relapsed/refractory MCL.

In February 2021, the NMPA approved a phase 3 clinical trial examining the use of ICP-022 in combination with R-CHOP in previously untreated patients with MCL. The primary end point of this study is PFS, and secondary end points include ORR, DOR, and overall survival.

A version of this article was originally published on OncLive as, “FDA Grants Breakthrough Therapy Designation to Orelabrutinib for Relapsed/Refractory MCL.”

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