The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study

Author:

Zelenetz Andrew D.1ORCID,Jurczak Wojciech2,Ribrag Vincent3,Linton Kim4,Collins Graham P.5,Jiménez Javier L.6,Bishton Mark7,Dholaria Bhagirathbhai8,Mengarelli Andrea9,Phillips Tycel J.10,Sungala Nagendraprasad11,Musuraca Gerardo12,Sheehy Oonagh13,Van Den Neste Eric14,Odera Mitsuhiko15,Miao Lu16,Gold Daniel P.16,Ghalie Richard G.16,Zinzani Pier L.17

Affiliation:

1. Memorial Sloan Kettering Cancer Center New York New York USA

2. Maria Sklodowska‐Curie National Research Institute of Oncology Krakow Poland

3. Gustave Roussy Cancer Villejuif France

4. The Christie NHS Foundation Trust and Manchester Cancer Research Centre Manchester UK

5. GenesisCare Cancer and Radiotherapy Centre Oxford UK

6. University Hospital Ramon y Cajal Madrid Spain

7. Translational Medical Sciences University of Nottingham and Nottingham University Hospitals NHS Trust Nottingham UK

8. Vanderbilt School of Medicine Nashville Tennessee USA

9. IRCCS Regina Elena National Cancer Institute Rome Italy

10. University of Michigan Health System Ann Arbor Michigan USA

11. Liverpool Hospital Sydney New South Wales Australia

12. Istituto Scientifico Romagnolo per lo Studio et la Cura dei Tumori Meldola Italy

13. Belfast HSC Trust Belfast United Kingdom

14. Cliniques Universitaires Saint‐Luc Bruxelles Belgium

15. Kyowa Kirin Co. Ltd. Tokyo Japan

16. MEI Pharma San Diego California USA

17. IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

Abstract

AbstractIn this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune‐related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow‐up of 14.3 months (range, 1–30.5), the median progression‐free survival was 11.6 months (95% CI, 8.3–not reached). Twenty‐one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class‐related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non‐infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class‐related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B‐cell malignancies.

Funder

Kyowa Kirin Pharmaceutical Development

MEI Pharma

Publisher

Wiley

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