Parsaclisib in Japanese patients with relapsed or refractory B‐cell lymphoma (CITADEL‐111): A phase Ib study

Parsaclisib, a potent, selective, next‐generation PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory B‐cell lymphoma. We undertook a phase Ib study (CITADEL‐111) evaluating safety, pharmacokinetics, and efficacy of parsaclisib in Japanese patients with relapsed or refractory B‐cell malignancies. Patients received oral parsaclisib daily for 8 weeks then once weekly (10‐mg dose, n = 3; 20‐mg dose, n = 14). Pharmacokinetic samples were collected on days 1, 8, and 15, and efficacy was monitored according to Lugano criteria. At data cut‐off (August 14, 2020), 6 patients (35.3%) remained on study treatment and 11 (64.7%) discontinued due to progressive disease (9 [52.9%]) or adverse events (2 [11.8%]). Median duration of treatment was 8.3 (range, 0.3–24.4) months. The most commonly reported nonhematologic adverse events were constipation (6 [35.3%]), nausea, and pyrexia (each 4 [23.5%]). Five patients (29.4%) experienced treatment‐emergent new or worsening decreased neutrophils to grade 3 or 4. No treatment‐emergent worsening in aminotransferase elevations to grade 3 or 4 were observed. Ten patients (58.8%) required dose interruption and 5 (29.4%) dose reduction. Body weight–normalized parsaclisib exposure was comparable between Japanese and Western patients. Objective response rate was 100% in follicular lymphoma (9 of 9 patients, including complete response in 2 patients [22.2%]) and marginal zone lymphoma (2 of 2 patients), and 16.7% in diffuse large B‐cell lymphoma (1 of 6 patients). Results observed in Japanese patients with relapsed or refractory follicular or marginal zone lymphoma support further clinical development of parsaclisib in these patient populations. We undertook a phase Ib study (CITADEL‐111) evaluating safety, pharmacokinetics, and efficacy of the potent and selective PI3Kδ inhibitor parsaclisib in Japanese patients with relapsed or refractory B‐cell malignancies. Objective response rate was 100% in follicular lymphoma (9 of 9 patients, including complete response in 2 patients [22.2%]) and marginal zone lymphoma (2 of 2 patients), and 16.7% in diffuse large B‐cell lymphoma (1 of 6 patients). Results observed in Japanese patients with relapsed or refractory follicular or marginal zone lymphoma support further clinical development of parsaclisib in these patient populations.