Zandelisib Elicits High Response Rates in Relapsed/Refractory Follicular Lymphoma

Zandelisib demonstrated significant activity and an encouraging preliminary safety profile in patients with relapsed/refractory follicular lymphoma who have received at least 2 prior systemic therapies.

Zandelisib demonstrated significant activity and an encouraging preliminary safety profile in patients with relapsed/refractory follicular lymphoma who have received at least 2 prior systemic therapies, according to topline findings from the phase 2 TIDAL study (NCT03768505).1

The results showed that after a minimum follow-up of 6 months, zandelisib monotherapy led to an Independent Review Committee–assessed objective response rate (ORR) of 70.3% (n = 64; 95% CI, 59.8%-79.5%) in the primary efficacy population (n = 91) and a complete response rate of 35.2% (95% CI, 25.4%-45.9%).

“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,” Daniel P. Gold, PhD, president and chief executive officer of MEI Pharma said in a news release. “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.”

Zandelisib is an investigational selective PI3Kδ inhibitor in clinical development for the treatment of patients with B-cell malignancies.

On March 31, 2020, the FDA granted zandelisib a fast track designation for the treatment of patients with relapsed/refractory follicular lymphoma who have received at least 2 prior systemic therapies.2

The ongoing global, open-label, pivotal phase 2 TIDAL trial is evaluating zandelisib monotherapy across 2 disease cohorts: the first cohort is enrolling patients with relapsed/refractory follicular lymphoma and the second cohort is enrolling patients with relapsed/refractory marginal zone lymphoma (MZL). In both cohorts, patients must have experienced disease progression on at least 2 prior systemic therapies, including chemotherapy and an anti-CD20 antibody.

ORR serves as the primary end point of the study, with a secondary end point of duration of response (DOR) in the primary efficacy population of patients with follicular lymphoma.

The follicular lymphoma cohort enrolled 121 patients, 91 of which were enrolled in the primary efficacy population. The median age of patients in this cohort was 64 years.

Patients enrolled in the primary efficacy follicular lymphoma and total patient populations received a median of 3 prior lines of therapy (range, 2-8).

Patients received zandelisib once daily for two 28-day cycles as response induction therapy followed by once daily dosing for the first 7 days of each subsequent 28-day cycle.

Enrollment in the follicular lymphoma cohort is complete; enrollment in the MZL cohort is ongoing.

Additional results showed that at a median follow-up of 8.4 months, the median DOR had not been reached with immature follow-up.

Consistent with findings from the phase 1b (NCT02914938) portion of the study, which evaluated zandelisib alone or in combination with rituximab (Rituxan) in patients with B-cell malignancies, zandelisib was generally well tolerated.

At a median follow-up of 9.4 months (range, 0.8-24) in the total study population (n = 121), treatment-related adverse effects (AEs) leading to discontinuation occurred in 9.9% of patients.

Grade 3 or greater adverse effects (AEs) of special interest included alanine aminotransferase/aspartate aminotransferase elevation (1.7%), colitis (1.7%), diarrhea (5%), mucositis (2.5%), pneumonitis (0.8%), and rash (3.3%).

“We are encouraged by the zandelisib data reported today from the TIDAL study,” said Yoshifumi Torii, PhD, executive officer, vice president, and head of the R&D Division of Kyowa Kirin. “Our team is continuing to study this investigational medicine with our partner MEI Pharma in the hopes of understanding zandelisib’s value and bringing more hope to lymphoma patients around the world.”

Full findings from the TIDAL study will be submitted for presentation at upcoming scientific meetings in 2022.

The randomized, phase 3 COASTAL study (NCT04745832) is also ongoing, which is investigating the safety and efficacy of zandelisib plus rituximab vs standard chemoimmunotherapy in patients with indolent non-Hodgkin lymphoma in first relapse.

The results of the COASTAL trial are intended to support full marketing applications in the United States and globally in patients with relapsed/refractory follicular lymphoma and MZL who have received at least 1 prior line of treatment. COASTAL is also intended to serve as the confirmatory trial for the potential FDA accelerated approval of zandelisib.3

References

  1. MEI Pharma and Kyowa Kirin announce data from the ongoing global phase 2 TIDAL study evaluating zandelisib as a single agent in patients with relapsed or refractory follicular lymphoma. News release. Mei Pharma. November 30, 2021. Accessed December 1, 2021. https://bit.ly/3E9hpOC
  2. MEI Pharma announces fast track designation granted by U.S. FDA for ME-401 for the treatment of adult patients with relapsed or refractory follicular lymphoma. News release. Mei Pharma. March 31, 2020. Accessed December 1, 2021. https://bit.ly/3ayo71X
  3. Zandelisib (ME-401). Mei Pharma. Accessed August 11, 2021. https://www.meipharma.com/pipeline/zandelisib