Orelabrutinib Lands FDA Breakthrough Therapy Designation for R/R MCL

The FDA has granted breakthrough therapy designation to orelabrutinib, a Bruton’s tyrosine kinase inhibitor, for the treatment of relapsed or refractory mantle cell lymphoma.

The FDA has granted breakthrough therapy designation (BTD) to orelabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of relapsed or refractory mantle cell lymphoma (R/R MCL), according to a press release by InnoCare Pharma.1

Orelabrutinib targets B-cell malignancies and autoimmune diseases. In late 2020, it was approved by the China National Medical Products Administration for both the treatment of patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. It was also approved in China for the treatment of R/R MCL.

"We are very proud that orelabrutinib was granted BTD after obtaining orphan drug designation. 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," said Jasmine Cui, PhD, the co-founder, chairwoman and chief executive officer of InnoCare, in a press release.

The BTD is based on phase 2 study (NCT04014205) of the agent in patients with R/R B-cell malignancies (NCT04014205). The open-label, multicenter, 2 stage study enrolled 106 patients across 22 centers in China. The primary end point was objective response rate (ORR). The secondary end points included safety determined by the incidence and severity of treatment-emergent adverse events and duration of response (DOR).

In order to participate, patients must be 18 years of age or older, have a histologically confirmed B-cell malignancy, have a life expectancy of 4 months or greater, an ECOG performance between 0 and 1, have adequate organ function, and negative tests results for hepatitis B virus (HBV), non-active HBV, or hepatitis C virus. Patients who are pregnant or breast feeding, have had prior treatment with systemic immunotherapeutic agents, prior treatment with any chemotherapeutic agent, a history of allogeneic stem-cell or other organ transplantation, active uncontrolled infections, or significant cardiovascular disease are not eligible to participate. 

As of May 2019, 62 patients had completed 6 cycles of treatment lasting 28 days each. The median duration of treatment was 197.5 days. The most common adverse event (AE) of any cause were mostly hematological including thrombocytopenia and neutropenia. However, respiratory infections and rash were also common. Grade 3 or higher thrombocytopenia occurred in 12.3% of patients. Hemorrhages rated grade 2 or higher were not reported. Additionally, no treatment-related grade 3 or higher gastrointestinal or cardio toxicity was noted. Twenty-five of 106 patients experienced a serious AE, 13 of which were treatment related.

The ORR was 82.5% and the complete response rate was 24.7%. The partial response rate was 57.7% and stable disease was observed in 9.3% of patients. The total DOR is 91.8%.2

1. InnoCare Announces Breakthrough Therapy Designation of Orelabrutinib by US FDA for Treatment of R/R MCL. News release. Innocare Pharma. June 28, 2021. Accessed June 28, 2021. https://bit.ly/3qIVyYF.
2. Song Y, Song Y,Liu L, et al. Safety and efficacy of orelabrutinib monotherapy in chinese patients with relapsed or refractory mantle cell lymphoma: A multicenter, open-label, phase II Study. Blood. 2019;134(suppl 1):755. doi: https://doi.org/10.1182/blood-2019-126305