Mocetinostat (MGCD0103), An Isotype-Selective Histone Deacetylase (HDAC) Inhibitor, Produces Clinical Responses In Relapsed/Refractory Hodgkin Lymphoma (HL): Update From a Phase II Clinical Study
Bibliographic record
Abstract
Abstract Abstract 1763 Background: HL patients with relapsed or refractory disease are incurable with standard therapies and new options are needed. Deregulation of HDAC activity can cause malignant diseases in humans. Mocetinostat inhibits Class I and IV HDACs and was shown to have preclinical and clinical activity. Methods: This was an open-label, Phase II trial in adults (≥18 years old) with relapsed/refractory HL. Patients initially received MGCD0103 at a starting dose of 110 mg (110 mg cohort) or 85 mg (85 mg cohort) 3x per week in 4-week cycles. Eligibility criteria included ≥1 target lesion (≥2 cm), no limit of prior therapies, ECOG status of 0–1, and platelet counts ≥25,000/μL. Tumor responses were determined every 8 weeks. The primary objective of this study was to estimate the treatment success rate defined as complete response (CR) + partial response (PR) + durable stable disease (SD for at least 6 cycles). Results: A total of 51 patients (23 patients in the 110 mg cohort and 28 patients in the 85 mg cohort) were enrolled (median age: 33 years old, range: 19–68 years old; gender: 29 male, 22 female; 84% caucasians; ECOG: 0: 49%, 1: 51%). Two patients experienced CR (110 mg cohort), 12 patients experienced PR (6 patients in each cohort) and 1 patient experienced durable SD (in the 85 mg cohort). The success rate was found to be 35% in the efficacy evaluable population (n=43) and 29% in the intent-to-treat population (n=51). Treatment-related adverse events of grade 3 or higher in ≥ 5% of patients included: thrombocytopenia (22%), fatigue (16%), neutropenia (14%), pneumonia (12%), anemia (10%), pericardial effusion (6%) and abnormal liver function tests (6%). Conclusions: Mocetinostat demonstrated single agent activity in heavily pretreated relapsed/refractory HL patients. The response rate reported in this study is among the best single agent activity described in HL with HDAC inhibitors, especially in the context of the minimal hematological toxicity observed. Despite the modest increased incidence of non-fatal pericardial effusions, the benefits of Mocetinostat outweigh the risks in this heavily pretreated patient population for which no curative options are available. Further development of Mocetinostat in HL is warranted, especially in less heavily treated patients and with prospective cardiac evaluations. Disclosures: Younes: Genentech: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; SBIO: Honoraria, Research Funding; Seattle Genetics: Honoraria, Research Funding. Kuruvilla:Hoffman Laroche: Honoraria, Research Funding; Celgene: Research Funding; Amgen: Honoraria; Otsuka: Honoraria; Genzyme: Honoraria. Drouin:Methylgene: Employment. Patterson:Methylgene: Employment. Besterman:Methylgene: Employment, Equity Ownership. Martell:Methylgene: Equity Ownership.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".