Contributions
Abstract: PB1566
Type: Publication Only
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Patients with follicular lymphoma (FL) who do not achieve a response after 2 or more prior lines of systemic therapy have a poor prognosis when treated with salvage chemotherapy alone or phosphoinositide 3-kinase (PI3K) inhibitors. Tazemetostat, a first-in-class, oral, selective enhancer of zeste homolog 2 (EZH2) inhibitor, has demonstrated single-agent antitumor activity and a favorable safety profile in patients with wild-type (WT) and mutant (MT) EZH2 relapsed/refractory (R/R) FL who had received ≥2 prior lines of therapy. Rituximab, as a single agent or in combination, is often used in the second line or later in patients with FL. In preclinical studies, tazemetostat has shown synergistic activity when combined with rituximab. This, in addition to clinical study experience with the combination of tazemetostat and rituximab in patients with diffuse large B-cell lymphoma, support the evaluation of tazemetostat in combination with rituximab in patients with R/R FL.
Aims
To determine the efficacy and safety of tazemetostat in combination with rituximab for the treatment of R/R FL.
Methods
This trial (NCT04762160) is a phase 2, single-arm, open-label, multicenter study of tazemetostat in combination with rituximab in patients with R/R FL who have received ≥2 prior lines of systemic therapy, including an anti-CD20–based regimen. Patients eligible for inclusion are aged ≥18 years with grade 1 to 3A FL who have met Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria to receive treatment, have an Eastern Cooperative Oncology Group (ECOG) performance score ≤2, and have not received any prior treatment with EZH2 inhibitors. Patients with transformed FL, a history of clinically significant gastrointestinal conditions, or any uncontrolled illness are excluded from this study. EZH2 mutation testing will be performed during patient screening; however, the presence of an EZH2 mutation is not required to be eligible for the study. Patients will receive tazemetostat 800 mg orally twice daily beginning on cycle 1 day 1 for continuous 28-day cycles until the end of cycle 24, for a total of 24 months of therapy. Patients will also receive rituximab 375 mg/m2 intravenously (IV) on cycle 1 day 1, then 375 mg/m2 IV or 1400 mg subcutaneously on days 8, 15, and 22 of cycle 1, and on day 1 of cycles 3, 4, 5, and 6, for a total of 8 doses of rituximab. The primary endpoint is the objective response rate (ORR; the proportion of patients with complete or partial response) in patients with WT EZH2. Key secondary endpoints include median progression free survival (PFS) in patients with WT EZH2; median PFS in all patients, regardless of mutational status; ORR in patients with MT EZH2; efficacy outcomes in rituximab-refractory patients; and incidence of adverse events. Efficacy and safety analyses will be performed on all patients who receive ≥1 dose of study drug. The evaluation of ORR will be based on Lugano 2014 response criteria and will be presented with corresponding 2-sided Clopper-Pearson 95% confidence intervals. The Kaplan-Meier method will be used to estimate PFS. Survival follow-up will be done following the study treatment period every 6 months for 2 years or until disease progression or death for all patients who complete the 24 months of tazemetostat therapy. As of February 2021, 1 site is recruiting patients in the United States, with 2 patients enrolled.
Results
N/A
Conclusion
N/A
Keyword(s): Follicular lymphoma, Non-Hodgkin's lymphoma, Rituximab
Abstract: PB1566
Type: Publication Only
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Patients with follicular lymphoma (FL) who do not achieve a response after 2 or more prior lines of systemic therapy have a poor prognosis when treated with salvage chemotherapy alone or phosphoinositide 3-kinase (PI3K) inhibitors. Tazemetostat, a first-in-class, oral, selective enhancer of zeste homolog 2 (EZH2) inhibitor, has demonstrated single-agent antitumor activity and a favorable safety profile in patients with wild-type (WT) and mutant (MT) EZH2 relapsed/refractory (R/R) FL who had received ≥2 prior lines of therapy. Rituximab, as a single agent or in combination, is often used in the second line or later in patients with FL. In preclinical studies, tazemetostat has shown synergistic activity when combined with rituximab. This, in addition to clinical study experience with the combination of tazemetostat and rituximab in patients with diffuse large B-cell lymphoma, support the evaluation of tazemetostat in combination with rituximab in patients with R/R FL.
Aims
To determine the efficacy and safety of tazemetostat in combination with rituximab for the treatment of R/R FL.
Methods
This trial (NCT04762160) is a phase 2, single-arm, open-label, multicenter study of tazemetostat in combination with rituximab in patients with R/R FL who have received ≥2 prior lines of systemic therapy, including an anti-CD20–based regimen. Patients eligible for inclusion are aged ≥18 years with grade 1 to 3A FL who have met Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria to receive treatment, have an Eastern Cooperative Oncology Group (ECOG) performance score ≤2, and have not received any prior treatment with EZH2 inhibitors. Patients with transformed FL, a history of clinically significant gastrointestinal conditions, or any uncontrolled illness are excluded from this study. EZH2 mutation testing will be performed during patient screening; however, the presence of an EZH2 mutation is not required to be eligible for the study. Patients will receive tazemetostat 800 mg orally twice daily beginning on cycle 1 day 1 for continuous 28-day cycles until the end of cycle 24, for a total of 24 months of therapy. Patients will also receive rituximab 375 mg/m2 intravenously (IV) on cycle 1 day 1, then 375 mg/m2 IV or 1400 mg subcutaneously on days 8, 15, and 22 of cycle 1, and on day 1 of cycles 3, 4, 5, and 6, for a total of 8 doses of rituximab. The primary endpoint is the objective response rate (ORR; the proportion of patients with complete or partial response) in patients with WT EZH2. Key secondary endpoints include median progression free survival (PFS) in patients with WT EZH2; median PFS in all patients, regardless of mutational status; ORR in patients with MT EZH2; efficacy outcomes in rituximab-refractory patients; and incidence of adverse events. Efficacy and safety analyses will be performed on all patients who receive ≥1 dose of study drug. The evaluation of ORR will be based on Lugano 2014 response criteria and will be presented with corresponding 2-sided Clopper-Pearson 95% confidence intervals. The Kaplan-Meier method will be used to estimate PFS. Survival follow-up will be done following the study treatment period every 6 months for 2 years or until disease progression or death for all patients who complete the 24 months of tazemetostat therapy. As of February 2021, 1 site is recruiting patients in the United States, with 2 patients enrolled.
Results
N/A
Conclusion
N/A
Keyword(s): Follicular lymphoma, Non-Hodgkin's lymphoma, Rituximab