Phase 2 studying findings presented at the 2021 European Hematology Association (EHA) Congress demonstrate the clinical efficacy of the PI3Kd inhibitor YY-20394 for the treatment of patients with relapsed or refractory (R/R) follicular lymphoma (FL).

“Although many new therapies are being investigated for patients with R/R FL, effective treatment options are very limited. The oral highly selective PI3Kd inhibitor YY-20394 was previously evaluated in a Phase1 dose escalation study, and demonstrated an acceptable safety profile and notable efficacy,” said Lugui Qiu, MD, Professor, General Medicine, Peking Union Medical Center, China, and co-investigators.

Thus, Dr Qiu et al aimed to evaluate the efficacy and safety of YY-20394 in patients with R/R FL with at least 2 prior systemic treatments.

As of the data cutoff of February 22, 2021, 93 patients with R/R FL received YY-20394 80mg orally once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal from the study. For 89 evaluable patients, efficacy was assessed according to IRWG criteria by the Independent Review Committee (IRC).

The median age of all patients was 50.4 years (29-78); 61.3% are male, 38.7% are female, and all are Asian. At baseline, most patients had an ECOG performance status of 0 (55.9%, 52-93) or 1 (40.9%, 38-93), were classified as Ann Arbor-Cotswolds stage III (21.5%, 20-90) or IV (73.1%, 68-93), and almost all patients (98.9%, 92-93) had grade 1, 2, or 3a FL. Only 1 patient developed grade 3b high-grade lymphoma. Patients received a median of 3 lines of prior treatment regimens, with 34 patients (34.6%) having received 4 or more. In all, 33% of patients (n=31) had refractory disease after their last treatment regimen. All patients received prior rituximab and alkylating agents. Just 3 patients (3.2%) underwent hematopoietic stem cell transplantation (HSCT).

A complete response (CR) was achieved in 11 patients (12.4%), partial response (PR) in 60 (67.4%), stable disease (SD) in 15 (16.1%), and progressive disease (PD) in 3 (3.2%), for an overall response rate (ORR) of 79.8% (95% CI, 58.5-83%) and a disease control rate (DCR) of 96.6%. The median time to response (TTR) was 1.87 months. The median time to disease progression was not determined due to 50.5% (n=47) of patients still receiving YY-20394 therapy.

Nearly two-thirds of patients had a treatment duration of more than 6 months as of the data cutoff. For 29 patients, the treatment duration was more than 300 days, with the longest being 637 days.

The most common nonhematologic TEAEs (all grades/grade ≥3) were pneumonia (24.7%/17.2%), ALT elevation (17.2%/2.2%), hypertriglyceridemia (23.7%/3.2%), hyperglycemia (18.3%/2.2%), rash (14.0%/2.2%), diarrhea (15.1%/1.1%), and pneumonitis (0%/5.4%). The most common grade ≥3 hematologic TEAEs included neutropenia (14%), thrombocytopenia (1.1%), and leukopenia (5.4%).

“YY-20394 is well tolerated with a promising objective response rates in patients with R/R FL,” concluded Dr Qiu et al.—Emily Bader

Qiu L, Wang T, Sun X, et al. A phase II study of a selective PI3Kd inhibitor YY-20394 in patients with relapsed or refractory follicular lymphoma. Presented at: the 2021 EHA Congress. June 9-17, 2021; virtual. Abstract EP792.