457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma
OBJECTIVES/GOALS: Primary Objective: To evaluate the safety of venetoclax plus tazemetostat in patients with relapsed and refractory (R/R) Follicular lymphoma (FL) or Diffuse large B-cell lymphoma (DLBCL) Secondary Objectives: 1. To evaluate the tolerability of the combination of T+V using patient r...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2024-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124003893/type/journal_article |
| _version_ | 1827296031236161536 |
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| author | Erin Mulvey Lisa Roth |
| author_facet | Erin Mulvey Lisa Roth |
| author_sort | Erin Mulvey |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: Primary Objective: To evaluate the safety of venetoclax plus tazemetostat in patients with relapsed and refractory (R/R) Follicular lymphoma (FL) or Diffuse large B-cell lymphoma (DLBCL) Secondary Objectives: 1. To evaluate the tolerability of the combination of T+V using patient reported outcomes (PROs) 2. To evaluate the efficacy of T+V METHODS/STUDY POPULATION: Study design: A phase I trial in two parts: Part 1: a single-arm, open-label sequential dose escalation (3+3) of venetoclax in combination with tazemetostat, given at its recommended phase II dose (RP2D) of 800mg BID, to determine the maximum tolerated dose (MTD) of venetoclax. Part 2: two expansion cohorts (R/R DLBCL and R/R FL) to further characterize the safety and tolerability of the combination, and to estimate the preliminary efficacy. We will perform additional exploratory studies to determine if there are biologic features that correlate with responses. Eligibility: up to 38 patients aged >/=18 years old with histologically confirmed diagnosis of FL or DLBCL who have received at least 2 prior lines of therapy for lymphoma with evidence of disease progression and meet inclusion criteria RESULTS/ANTICIPATED RESULTS: Primary Endpoints: 1. Incidence and severity of adverse events as per CTCAEv5 2. Dose-limiting toxicity (DLT) of T+V, and to establish the maximum tolerated dose (MTD) of V plus fixed dose T Secondary Endpoints: 1. Incidence and Severity of toxicity and quality of life as per PRO-CTCAE and FACT-Lym 2. Overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, as per Lugano criteria 3. Duration of response (DOR), progression-free survival (PFS), overall survival (OS)Exploratory Endpoints: 1. Characterization of tumor cells pre-treatment (including EZH2 mutations and BCL2 translocations) 2. Phenotypic analysis (including BCL2 expression) and quantification of the tumor microenvironment in pre-treatment samples (using image mass cytometry)Explorato DISCUSSION/SIGNIFICANCE: There is a need for novel therapeutic approaches to improve the prognosis for patients with R/R NHL. Preclinical data suggests synergism between the pair.5 Importantly, this represents a chemotherapy-free, oral regimen. If well tolerated, this could present an alternative therapeutic option for patients ineligible for more intensive therapies. |
| first_indexed | 2024-04-24T14:32:09Z |
| format | Article |
| id | doaj.art-8127e033996848169631fb0f0c819869 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-24T14:32:09Z |
| publishDate | 2024-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-8127e033996848169631fb0f0c8198692024-04-03T02:00:25ZengCambridge University PressJournal of Clinical and Translational Science2059-86612024-04-01813513510.1017/cts.2024.389457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin LymphomaErin Mulvey0Lisa Roth1Weill Cornell Medical CollegeWeill Cornell Medical CollegeOBJECTIVES/GOALS: Primary Objective: To evaluate the safety of venetoclax plus tazemetostat in patients with relapsed and refractory (R/R) Follicular lymphoma (FL) or Diffuse large B-cell lymphoma (DLBCL) Secondary Objectives: 1. To evaluate the tolerability of the combination of T+V using patient reported outcomes (PROs) 2. To evaluate the efficacy of T+V METHODS/STUDY POPULATION: Study design: A phase I trial in two parts: Part 1: a single-arm, open-label sequential dose escalation (3+3) of venetoclax in combination with tazemetostat, given at its recommended phase II dose (RP2D) of 800mg BID, to determine the maximum tolerated dose (MTD) of venetoclax. Part 2: two expansion cohorts (R/R DLBCL and R/R FL) to further characterize the safety and tolerability of the combination, and to estimate the preliminary efficacy. We will perform additional exploratory studies to determine if there are biologic features that correlate with responses. Eligibility: up to 38 patients aged >/=18 years old with histologically confirmed diagnosis of FL or DLBCL who have received at least 2 prior lines of therapy for lymphoma with evidence of disease progression and meet inclusion criteria RESULTS/ANTICIPATED RESULTS: Primary Endpoints: 1. Incidence and severity of adverse events as per CTCAEv5 2. Dose-limiting toxicity (DLT) of T+V, and to establish the maximum tolerated dose (MTD) of V plus fixed dose T Secondary Endpoints: 1. Incidence and Severity of toxicity and quality of life as per PRO-CTCAE and FACT-Lym 2. Overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, as per Lugano criteria 3. Duration of response (DOR), progression-free survival (PFS), overall survival (OS)Exploratory Endpoints: 1. Characterization of tumor cells pre-treatment (including EZH2 mutations and BCL2 translocations) 2. Phenotypic analysis (including BCL2 expression) and quantification of the tumor microenvironment in pre-treatment samples (using image mass cytometry)Explorato DISCUSSION/SIGNIFICANCE: There is a need for novel therapeutic approaches to improve the prognosis for patients with R/R NHL. Preclinical data suggests synergism between the pair.5 Importantly, this represents a chemotherapy-free, oral regimen. If well tolerated, this could present an alternative therapeutic option for patients ineligible for more intensive therapies.https://www.cambridge.org/core/product/identifier/S2059866124003893/type/journal_article |
| spellingShingle | Erin Mulvey Lisa Roth 457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma Journal of Clinical and Translational Science |
| title | 457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma |
| title_full | 457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma |
| title_fullStr | 457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma |
| title_full_unstemmed | 457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma |
| title_short | 457 A Phase I Trial of Tazemetostat and Venetoclax in Relapsed and Refractory non-Hodgkin Lymphoma |
| title_sort | 457 a phase i trial of tazemetostat and venetoclax in relapsed and refractory non hodgkin lymphoma |
| url | https://www.cambridge.org/core/product/identifier/S2059866124003893/type/journal_article |
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