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TopoTarget has announced positive data from a phase I study of belinostat given as oral monotherapy day 1-14 every three weeks in patients with lymphoma presented at the ASCO (American Society of Clinical Oncology) annual conference May 29 - Jun 2
Copenhagen, Denmark | May 30, 2009 | TopoTarget A/S (OMX: TOPO) has announced positive data from a phase I study of belinostat given as oral monotherapy day 1-14 every three weeks in patients with lymphoma presented at the ASCO (American Society of Clinical Oncology) annual conference May 29 - Jun 2. Oral belinostat can be delivered safely to lymphoma patients in doses that are higher than the maximum tolerated dose for patients with solid tumors. Current dose level is 1500 mg daily with 5 patients still ongoing. Despite extensive pre-treatment, 7 of 10 evaluable patients have achieved stabilization of disease for up to nine months. Early onset of tumor shrinkage has been seen in patients with Hodgkin's disease and Mantle cell lymphoma. The acceptable safety profile and early tumor shrinkage noted warrants continued evaluation of belinostat in lymphoma, especially in combination with other active compounds.
“These new positive data demonstrate that the oral form of belinostat can be administered in higher doses than previously reported in solid tumors. Belinostat has already at this stage and despite extensive prior treatments in 7 out of 10 evaluable patients achieved disease control for up to 9 months. These findings and the flexibility in optimizing the dose to the cancer patients is important for this new drug class”, says professor Peter Buhl Jensen, CEO of TopoTarget.
The study:
A phase I, open label, dose-escalation, multi-center study. Objectives are to determine safety and dose limiting toxicity (DLTs) for oral belinostat in patients with relapsed/refractory lymphoma and to assess preliminary efficacy.
Belinostat treatment included day 1 to 14, once daily administration every 21 days with doses escalated in steps of 250 mg from 750 mg to current level of 1500 mg.
Results:
15 patients, median age 53 have been treated. Most common lymphoma types are Mantle cell lymphoma (33%), Hodkin's disease (33%) and Cutaneous T-cell lymphoma (13%). Most frequent related adverse events were anorexia, diarrhea fatigue and vomiting as we know them from other studies of belinostat. Hematological toxicity has been mild. The patients had in general been treated with prior multiple lines of therapy median 4 (range 1-12). Stable disease (SD) seen in 7 of 10 extensive pre-treated evaluable patients, including 3/3 patients with Mantle cell lymphoma, 3/4 patients with Hodgkin's disease, and the only evaluable patient with Cutaneous T-cell lymphoma (previously progressing on Vorinostat). Median treatment duration for patients with SD is currently +77 days (range 62 to +282 days; 3 patients in ongoing treatment).
Even though no partial remissions (PRs) have been noted according to the International Working Group criteria (Cheson 2007), tumor shrinkage of 43 to 49% has been observed in 1 patient with Hodgkin's disease and 2 of 3 evaluable patients with Mantle cell lymphoma, after two cycles of therapy (first assessment time point).
Conclusions:
Oral belinostat can be delivered safely with a day 1 to 14, q3 weekly, schedule in patients with lymphoma. This dose is higher than the dose that has been established for patients with solid tumors. No Dose limiting toxicities (DLTs) have been seen at dose levels 750 to 1250 mg daily. At the current dose level of 1500 mg daily 1 patient has experienced a DLT, thus the cohort has been expanded. Most common adverse events have been anorexia, diarrhea, fatigue, and vomiting. Hematological toxicity has been mild. Despite extensive pre-treatment 7 of 10 currently evaluable patients have achieved stabilization of disease for up to nine months. Early onset tumor shrinkage has been seen in patients with Hodgkin's disease and Mantle cell lymphoma. The acceptable safety profile and early tumor shrinkage noted in Mantel cell lymphoma and Hodgkin's disease warrants continued evaluation of belinostat in lymphoma, especially in combination with other active compounds.
SOURCE: TopoTarget A/S |
