Isotype-selective histone deacetylase (HDAC) inhibitor MGCD0103 demonstrates clinical activity and safety in patients with relapsed/refractory classical Hodgkin Lymphoma (HL)

Abstract

8507 Background: With no approved post-transplant therapies, HL patients (pts) with relapsed or refractory disease have poor prognosis. MGCD0103 is an oral isotype-selective inhibitor of histone deacetylases (HDACs) with significant preclinical and clinical activity in hematopoietic cancers. Methods: Open-label, Phase II trial in adults with relapsed/refractory HL (Trial 010); most with prior transplant. Pts received MGCD0103 at 110 or 85 mg 3x per week in 4-week cycles. Plasma Thymus and Activation Regulated Chemokine (TARC) levels were determined by ELISA. Responses were assessed by CT and PET. Results: 33 pts have been enrolled to date (median age, 31 yrs; range, 19–62 yrs) of which 29 (88%) had prior transplant. Among 23 pts in the 110 mg cohort, 21 were evaluable, of whom 2 (10%) had a complete response (CR) and 6 (29%) had a partial response (PR) for an overall response (OR) rate of 38% (median time to response, 2 cycles). The 2 pts with CR had progression free survival lasting >270 and >420 days with both responses ongoing. One additional pt (5%) had SD >6 cycles. Among 10 pts in the 85 mg cohort, 5 were evaluable for efficacy, all of whom had tumor reductions of ≥30%, including 1 PR and 2 SDs (45% and 49% tumor reduction). Comparison between 85 and 110 mg revealed 20% and 39% of pts respectively with ≥ grade 3 toxicity. Decrease in Day 8 plasma TARC levels correlated with clinical response (PR+CR). Conclusions: MGCD0103 demonstrated significant anti-tumor activity in relapsed/refractory post-transplant HL. The 85 mg dose exhibited meaningful activity and may be better tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MethylGene Inc., Pharmion Corporation MethylGene Inc. MethylGene Inc.