On June 4, 2022 MEI Pharma, Inc. (NASDAQ: MEIP), a latestage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions utilizing the latest biotechnology, reported data from the ongoing Phase 2 TIDAL study evaluating the intermittent dosing of zandelisib, an orally administered investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor in clinical development for the treatment of B-cell malignancies, is highlighted in a poster and oral discussion session at the of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting(Press release, Kyowa Hakko Kirin, JUN 4, 2022, View Source [SID1234615564]).
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"The Phase 2 TIDAL data generated to date continue to highlight zandelisib’s therapeutic profile and the potential to benefit patients, supporting our commitment to advancing the program and our already ongoing randomized Phase 3 COASTAL study with our partner, Kyowa Kirin," said Richard Ghalie, M.D., chief medical officer of MEI Pharma. "In light of the promising results from TIDAL to date, we remain committed to the zandelisib program with our primary focus being on COASTAL, our ongoing Phase 3, randomized, study evaluating zandelisib in combination with rituximab in follicular and marginal zone lymphoma patients with at least one prior line of therapy."
"We are very pleased to present data from Phase 2 TIDAL study in ASCO (Free ASCO Whitepaper) meeting," said Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. We continue to see favorable profile of zandelisib that balances efficacy and safety. We remain committed to maximizing the value of zandelisib in B-cell malignancies with our partner MEI Pharma."
Clinical Data from the Phase 2 TIDAL Study Evaluating Zandelisib in Patients with Relapsed or Refractory Follicular Lymphoma
• Presentation Title: Efficacy and safety of zandelisib administered by intermittent dosing (ID) in patients with relapsed or refractory (R/R) follicular lymphoma (FL): Primary analysis of the global phase 2 study TIDAL
• Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
• Presenter: Andrew David Zelenetz, Ph.D., M.D.
• Date and Time: Saturday, June 4, 2022, at 3:00 Central Time
• Poster ID: 7511 / 165
Study Details The ongoing TIDAL study (NCT03768505) is a global, open-label Phase 2 trial evaluating zandelisib as a single agent in two disease cohorts: one in relapsed or refractory (r/r) follicular lymphoma (FL) and one 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. 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 (ID). Enrollment in the FL cohort is complete; enrollment in the MZL cohort is ongoing.
The FL cohort enrolled a total of 121 patients, with the first 91 consisting of the primary efficacy population (PEP) for the evaluation of overall response rate (ORR) and duration of response (DOR).
The median age of patients enrolled with FL was 64 years old. Enrolled patients were generally heavily pretreated; the median number of prior therapies was 3 (range 2-8) and 96% of patients had received prior chemoimmunotherapy. Further, 28 patients (23%) received prior stem cell transplant, 50 patients (41%) were refractory to last therapy, 41 patients (34%) had tumors ≥5 cm, and 68 patients (56%) were POD24 (progression of disease within 24 months of prior chemoimmunotherapy). The primary efficacy endpoint is ORR as assessed by independent review committee (IRC) using a modified Lugano criteria. The data cutoff date is September 30, 2021, approximately 6 months after the last patient in the PEP received their first dose of zandelisib. Data from the enrolling MZL cohort is not reported.
Efficacy The primary endpoint of ORR of zandelisib as a single agent in the PEP was 70.3% (N=64), 95% CI=59.8, 79.5, as assessed by IRC; the complete response rate was 35.2% (N=32), 95% CI=25.4, 45.9. Responses across sub-groups (i.e. response to last treatment, number of prior therapies and POD24) were all >63%. Response Rates by Independent Review Committee in All PEP Patients and by Subgroup Response to Last Treatment Number of Prior Therapies POD24 n(%) Efficacy Population (n=91) Relapsed (n=49) Refractory (n=42) 2 (n=42) >2 (n=49) Yes (n=51) No (n=40) ORR (CR or PR) 64 (70.3) 37 (75.5) 27 (64.3) 33 (78.6) 31 (63.3) 34 (66.7) 30 (75.0) CR 32 (35.2) 20 (40.8) 12 (28.6) 18 (42.9) 14 (28.6) 16 (31.4) 16 (40.0) CR, complete response; PEP, primary efficacy population; POD24 progression of disease within 24 months; PR, partial response. Responses were first observed in the first two cycles of therapy in 87.5% of all responses (N=56) and 75% of all CRs (N=24) were observed in the first four cycles. As of the data cutoff date, the data are not sufficiently mature to accurately estimate the final DOR in the PEP.
Safety and Tolerability With a median follow-up of 9.4 months (range 0.8-24) in the safety population of 121 patients, 9.9% (N=12) of patients had discontinued therapy due to any drug-related adverse event. Grade 3 adverse events of special interest (AESI) were diarrhea in 5% (N=6), colitis in 1.7% (N=2), cutaneous rash in 3.3% (N=4), stomatitis in 2.5% (N=3), and 0.8% (N=1) each for AST and ALT elevation, and non-infectious pneumonitis. Grade 3 AESIs primarily (83%, 15 of 18) occurred in cycles 1-3, with only 3 cases reported on ID in Cycles ≥4. No Grade 4 or Grade 5 AESI were recorded. Cumulative Incidence of Time to First Occurrence of Grade 3 AESI Treatment-emergent COVID-19 infections were reported in 8.3% (N=10) of patients, and 8.3% (N=10) of patients reported other Grade 3 infections. Four COVID infections were fatal, as were 1 case each of pneumonia and Tumor Lysis Syndrome About Zandelisib Zandelisib, a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, treatment for patients with B-cell malignancies. Clinical trials are investigating the efficacy and safety of zandelisib as a single agent and in combination with other modalities while administered on an Intermittent Dosing Regimen (ID) and in a timelimited manner when dosed in combination. The ID leverages molecular and biologic properties specific to zandelisib. In November 2021, MEI Pharma and Kyowa Kirin announced topline data from ongoing Phase 2 TIDAL study (NCT03768505) evaluating zandelisib as a single agent for follicular lymphoma (FL) patients who received at least two prior systemic therapies. Zandelisib demonstrated a 70.3% objective response rate (ORR) as determined by an Independent Review Committee (IRC) assessment in the primary efficacy population (n=91). In addition, 35.2% of patients achieved a complete response. At the time of the data cutoff, the data were 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 (n=121), interim data demonstrated a discontinuation rate due to any drug related adverse event of 9.9%.
Patients enrolled in the study will continue to be followed for safety and DOR. Ongoing zandelisib studies include the cohort in TIDAL evaluating patients with r/r marginal zone lymphoma (MZL) and continuing evaluation of the cohort of patients in the study with r/r FL. Also ongoing is the Phase 3 COASTAL study (NCT04745832), comparing zandelisib plus rituximab to standard of care chemotherapy plus rituximab in patients with r/r FL or MZL who received more than one prior line of therapy, which must have included an anti-CD20 antibody in combination with chemotherapy or lenalidomide. COASTAL, which is also evaluating timelimited intermittent administration of zandelisib, is intended to support marketing applications in the U.S. and globally. Other ongoing studies include a Phase 2 pivotal study in Japan (NCT04533581) in patients with indolent B-cell non-Hodgkin’s lymphoma (iB-NHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) conducted by Kyowa Kirin. In March 2020, the FDA granted zandelisib Fast Track designation for the treatment of adult patients with r/r follicular lymphoma who have received at least two prior systemic therapies. In November 2021, the FDA granted zandelisib Orphan Drug designation 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 U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S. About Follicular Lymphoma Follicular lymphoma (FL) is the most common indolent lymphoma, comprising about 20-30% of all non-Hodgkin lymphomas (NHL).
The disease also develops in B lymphocytes, is chronic in most cases and tends to progress slowly. Most people diagnosed with FL are over 65 years of age. Sometimes follicular lymphomas can transform into a more aggressive form of large B-cell lymphoma, a fast-growing (aggressive) type of NHL.