Announcement No. 24-09 / Copenhagen, 30 May 2009
TopoTarget A/S
Symbion
Fruebjergvej 3
DK 2100 Copenhagen
Denmark
Tel: +45 39 17 83 92
Fax: +45 39 17 94 92
CVR-nr: 25695771
www.topotarget.com
Copenhagen, Denmark - 30 May 2009 - TopoTarget A/S (OMX: TOPO) has announced
that positive data from a phase 2 study of belinostat monotherapy in patients
with thymic malignancies was presented on 30 May at the ASCO 2009 conference
held from 29 May - 2 June. A total of 27 patients were evaluable for response.
In two out of 17 patients with thymoma a partial response was documented (13
and 13+ months), and in addition 11 patients had stable disease (4-15+ months).
No response was seen in 10 patients with thymic carcinoma. The conclusion is
that belinostat has activity in patients with recurrent or refractory thymoma.
The thymoma cohort has been expanded to the second stage of the study and
enrollment is ongoing. The study is sponsored by the Cancer Therapy Evaluation
Program at the National Cancer Institute (NCI, US) under a Clinical Trials
Agreement with TopoTarget for the development of belinostat.
“The data presented at ASCO concludes that belinostat has activity in patients
with recurrent or refractory thymoma - a disease where there is a need for new
treatment options. The thymoma cohort has been expanded to the second stage of
the study” says study principal investigator Professor Giuseppe Giaccone,
Branch Chief, Medical Oncology Branch, National Cancer Institute, Bethesda, MD,
USA.
Thymic malignancies are rare tumors of the anterior mediastinum. Platinum-based
chemotherapy is used for first-line treatment of advanced disease. About 50% of
patients with advanced disease may fail initial therapy. There is no
established role of second-line therapy in patients with refractory or
recurrent disease. Belinostat is evaluated as treatment for recurrent thymic
malignancies in the reported study based on a good pre-clinical rationale and a
prolonged minor response (31 months) seen in a patient with recurrent thymoma
participating in a belinostat phase I study.
The study:
Patients with recurrent thymoma or thymic carcinoma, progressing after
platinum-based chemotherapy were eligible. They were required to have
measurable disease, PS 0-2 and normal organ functions. Belinostat was given as
a 30-minutes intravenous infusion at 1000 mg/m2 once daily on days 1 to 5 of a
21-day cycle until disease progression or intolerable side effects. For
patients who had received more than 12 cycles of therapy, belinostat was
administered every 28 days.
Results:
From December 2007 to May 2009, 32 patients with thymic malignancies have been
enrolled at 2 institutions; 18 patients were males. The median age is 53.5
years (24-84), 21 thymomas and 11 thymic carcinomas. Mean number of prior
regimens was 3 (1-10). 19 patients underwent prior tumor resection and 4 had
myasthenia gravis. A median of 4 cycles of belinostat has been administered
(1-20+). Treatment was well tolerated, with nausea being the most common side
effect and well controlled with prophylactic antiemetics. 27 patients are
evaluable for response: 2 had a partial response (13, 13+ m), 15 stable disease
(3-15+ m) and 10 progression. No responses were seen in 10 evaluable patients
with thymic carcinomas.
Correlative markers of activity in blood and tumor were performed. Tubulin and
lysine protein acetylation was generally observed in peripheral blood one hour
after belinostat infusion on day 3 of the first cycle. In 9/9 patients analyzed
for acetylated lysine at baseline and 1 hour post-infusion on day 3 of the
first cycle, a response of between 2.2-fold and 10.4-fold over baseline was
observed. In 5/5 patients analyzed at the same time points for acetylated
tubulin, a response of between 2.1-fold and 8.9-fold over baseline was
observed. Other correlative markers are being analyzed.
Conclusions:
Belinostat has activity in patients with recurrent or refractory thymoma. The
thymoma cohort has been expanded to the second stage of the study and
enrollment is ongoing.
TopoTarget A/S
For further information, please contact:
Peter Buhl Jensen Telephone +45 39 17 94 99
CEO Mobile +45 21 60 89 22
