Contributions
Abstract: EP792
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Although many new therapies are being investigated for patients with relapsed/recurrent (/r) follicular lymphomas (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. In this study, we report on the topline data from an ongoing Phase 2 study of YY-20394 under investigation in patients with relapsed or refractory FL with at least 2 prior systemic treatments.
Aims
To evaluate the efficacy and safety of YY-20394 in FL patients.
Methods
Informed consent was obtained for all patients of the study. YY-20394 was given 80 mg orally once daily (QD) with 28 days cycle until disease progression, unacceptable toxicity or withdrawal from the study. Adverse events (AEs) were graded by NCI-CTCAE v5.0. Efficacy was assessed according to IRWG criteria by the Independent Review Committee (IRC).
Results
As of a data cut-off of February 22, 2021, the study was fully enrolled (93 patients) with 89 patients evaluable for efficacy. For the 93 r/r FL patients, the median age is 50.4 years (range 29-78); 61.3% (57/93) are male and 38.7% (36/93) are female and all are Asian. At baseline, the majority of patients had an ECOG performance status of 0 (55.9%, 52/93) or 1 (40.9%, 38/93) and were classified as Ann Arbor-Cotswolds stage III (21.5%, 20/93) or IV (73.1%, 68/93). Nearly all patients (98.9%, 92/93) had grade 1, 2, or 3a FL; only 1 out of 93 patients had transformed to grade 3b high-grade lymphoma. Patients had received a median of three lines of prior treatment regimens (range 2-20), with 34 patients (34.6%) having received four or more lines of prior treatment regimens. Thirty-three percent of patients (31 out of 93 patients) had refractory disease after their last treatment regimen. All patients had received prior rituximab and alkylating agents. Three patients (3.2%) had undergone HSCT.
For the 89 evaluable patients, efficacy was determined by IRC. Complete response (CR) were 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% confidence interval [CI] 58.5-83.0%) and a disease control rate (DCR) of 96.6%. The median time to response (TTR) is 1.87 months (range 1.66-5.60 months). All the patients have had at least 6 months of follow-up. The median time to disease progression has not been determined yet because 50.5% (47 out of 93) patients are still receiving YY-20394 treatment, and nearly two thirds of the 93 patients had a treatment duration of ＞6 months at the cut-off date. The treatment duration for 29 subjects were more than 300 days, with the longest treatment duration of 637 days to date.
Among all 93 enrolled patients with r/r FL in the phase II study, 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%）, pneumonitis (0%/5.4%). Gr≥3 hematologic TEAEs were neutropenia (14.0%), thrombocytopenia 1.1%),) and leukopenia (5.4%).
Conclusion
YY-20394 is well tolerated with a promising objective response rates in patients with relapsed or refractory follicular lymphoma. Clinical trial information: NCT04370405
Keyword(s): Follicular lymphoma, PI3 kinase
Abstract: EP792
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Although many new therapies are being investigated for patients with relapsed/recurrent (/r) follicular lymphomas (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. In this study, we report on the topline data from an ongoing Phase 2 study of YY-20394 under investigation in patients with relapsed or refractory FL with at least 2 prior systemic treatments.
Aims
To evaluate the efficacy and safety of YY-20394 in FL patients.
Methods
Informed consent was obtained for all patients of the study. YY-20394 was given 80 mg orally once daily (QD) with 28 days cycle until disease progression, unacceptable toxicity or withdrawal from the study. Adverse events (AEs) were graded by NCI-CTCAE v5.0. Efficacy was assessed according to IRWG criteria by the Independent Review Committee (IRC).
Results
As of a data cut-off of February 22, 2021, the study was fully enrolled (93 patients) with 89 patients evaluable for efficacy. For the 93 r/r FL patients, the median age is 50.4 years (range 29-78); 61.3% (57/93) are male and 38.7% (36/93) are female and all are Asian. At baseline, the majority of patients had an ECOG performance status of 0 (55.9%, 52/93) or 1 (40.9%, 38/93) and were classified as Ann Arbor-Cotswolds stage III (21.5%, 20/93) or IV (73.1%, 68/93). Nearly all patients (98.9%, 92/93) had grade 1, 2, or 3a FL; only 1 out of 93 patients had transformed to grade 3b high-grade lymphoma. Patients had received a median of three lines of prior treatment regimens (range 2-20), with 34 patients (34.6%) having received four or more lines of prior treatment regimens. Thirty-three percent of patients (31 out of 93 patients) had refractory disease after their last treatment regimen. All patients had received prior rituximab and alkylating agents. Three patients (3.2%) had undergone HSCT.
For the 89 evaluable patients, efficacy was determined by IRC. Complete response (CR) were 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% confidence interval [CI] 58.5-83.0%) and a disease control rate (DCR) of 96.6%. The median time to response (TTR) is 1.87 months (range 1.66-5.60 months). All the patients have had at least 6 months of follow-up. The median time to disease progression has not been determined yet because 50.5% (47 out of 93) patients are still receiving YY-20394 treatment, and nearly two thirds of the 93 patients had a treatment duration of ＞6 months at the cut-off date. The treatment duration for 29 subjects were more than 300 days, with the longest treatment duration of 637 days to date.
Among all 93 enrolled patients with r/r FL in the phase II study, 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%）, pneumonitis (0%/5.4%). Gr≥3 hematologic TEAEs were neutropenia (14.0%), thrombocytopenia 1.1%),) and leukopenia (5.4%).
Conclusion
YY-20394 is well tolerated with a promising objective response rates in patients with relapsed or refractory follicular lymphoma. Clinical trial information: NCT04370405
Keyword(s): Follicular lymphoma, PI3 kinase