MEI Pharma and Kyowa Kirin Report Data from Study Evaluating Zandelisib in Patients with Relapsed or Refractory Follicular Lymphoma
November 30, 2021
MEI Pharma and Kyowa Kirin said that the pivotal phase 2 TIDAL study evaluating zandelisib as a single agent for follicular lymphoma patients who received at least two prior systemic therapies demonstrated a 70.3 percent objective response rate (ORR) as determined by Independent Review Committee (IRC) assessment in the primary efficacy population.
In addition, 35.2 percent of patients achieved a complete response. The data are currently insufficiently mature to accurately estimate duration of response (DOR). In line with previously reported data from the phase 1b study, zandelisib was generally well tolerated. With 9.4 months (range: 0.8-24) median duration of follow-up in the total study population, interim data demonstrated a discontinuation rate due to any drug related adverse event of 9.9 percent. Patients enrolled in the study will continue to be followed for safety and DOR.
“The emerging zandelisib data are very promising and indicate the potential to positively impact the standard-of-care for patients with relapsed or refractory follicular lymphoma,” said Daniel Gold, president and CEO of MEI Pharma. “The response data and interim safety data reported today support our plans to continue discussions with the FDA on timing of an accelerated approval submission, and we look forward to reporting a more comprehensive review of the data at upcoming medical conferences while continuing this trial and continuing to advance the zandelisib clinical development program in indications beyond follicular and marginal zone lymphomas with our partner, Kyowa Kirin.”
Although rare, follicular lymphoma (FL) is the most common indolent lymphoma, comprising about 20-30 percent of all non-Hodgkin lymphomas (NHL). The disease also forms on B-cells, is chronic in most cases and tends to progress slowly. Follicular lymphoma is most common in the elderly, having a median age at diagnosis of approximately 65 years old. Sometimes follicular lymphomas can transform into a more aggressive form of large B-cell lymphoma, a fast-growing type of NHL.
Zandelisib is an experimental selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor in clinical development for the treatment of B-cell malignancies. It is being developed as an oral, once-daily, treatment for patients with B-cell malignancies as a single agent and in combination with other modalities. The U.S. Food and Drug Administration has granted zandelisib Orphan Drug and Fast Track designations for the treatment of patients with follicular lymphoma.
In April 2020, MEI and Kyowa Kirin entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin will co-develop and co-promote zandelisib in the United States, with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the United States.
The ongoing TIDAL study is a global, open-label phase 2 trial evaluating zandelisib as a single agent across two disease cohorts: the first cohort for the treatment of adults with relapsed or refractory (r/r) FL and the second cohort for r/r marginal zone lymphoma (MZL), in both cases after failure of at least two prior systemic therapies, including chemotherapy and an anti-CD20 antibody. Enrollment in the FL cohort is complete; enrollment in the MZL cohort is ongoing. Subject to the results and discussion with the FDA, TIDAL study data from each study cohort are intended to be submitted to the FDA to support accelerated approval marketing applications.
The r/r FL cohort enrolled a total of 121 patients, 91 of which were enrolled in the primary efficacy population for the evaluation of ORR and DOR. The median age of patients with FL was 64 years old. Patients enrolled in both the FL primary efficacy and total patient populations received a median of 3 prior lines of treatment (range: 2-8). Patients were administered zandelisib once daily for two 28-day cycles as response induction therapy, followed thereafter by once daily dosing for the first seven days of each subsequent 28-day cycle, a schedule called Intermittent Dosing Therapy (IDT).
The ORR in the 91 patients with r/r FL enrolled in the primary efficacy population was 70.3 percent, as assessed by IRC after a minimum follow-up of 6 months. The complete response rate was 35.2 percent. The ORR represents the primary endpoint of the TIDAL study.
As of the data cutoff date, the data are not sufficiently mature to accurately estimate the final DOR in the FL primary efficacy population, a secondary outcome measure of the TIDAL study. However, with a median follow-up time for response of 8.4 months, the median DOR had not been reached. The data cutoff date is approximately 6 months after the last patient in the primary efficacy population received their first dose of zandelisib.
Zandelisib appeared generally well-tolerated in the total TIDAL study population through the data cutoff date. The safety observed in TIDAL was consistent with data previously reported from the phase 1b study evaluating zandelisib in patients with B-cell malignancies as a single agent or in combination with rituximab.
A more complete report of the TIDAL data as of the data cutoff date will be submitted for presentation at upcoming scientific congresses in 2022.
Author: Rare Daily Staff
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