Positive data on oral belinostat in phase I dose escalating study in solid tumors presented at ASCO

Announcement No. 22-09 / Copenhagen, 29 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 - 29 May 2009 - TopoTarget A/S (OMX: TOPO) has announced
positive data from a phase I study of belinostat given as oral monotherapy in
three different schedules (A) continuous daily dosing; (B) daily dosing on day
1-14 every 3 weeks; C) daily dosing day 1-5 every 3 weeks) in patients with
solid tumors. Oral belinostat can be delivered safely in multiple schedules.
Despite a median of 3 prior lines of therapy 48 (64%) of 75 evaluable patients
achieved tumor growth control (SD), 15 patients had a treatment duration ≥ 3
months. The safety profile and long stabilizations in multiple tumor types
makes belinostat an interesting option for further evaluation as a monotherapy
and in combination with chemotherapy. 


“These new data demonstrate an increased utility of belinostat which now can be
administered both as IV and oral allowing maximum flexibility for optimizing
the use of this important new drug class”, says professor Peter Buhl Jensen,
CEO of TopoTarget. 

“We look forward to obtain data from the CUP* phase II randomized study where
this principle is introduced (BelCaP versus carboplatin and paclitaxel, BelCaP
= belinostat with carboplatin and paclitaxel) in solid tumors where belinostat
is given as IV on the first three days and followed up by oral belinostat the
remaining two days in a five days treatment every three weeks” Peter Buhl
Jensen further comments. 

*CUP= Cancer of Unknown Primary site

The study:
Phase I dose escalating trial of belinostat in patients with solid tumors.
Patients were treated with multiple schedules A) continuous dosing x 1 or 2
daily; B) 1 or 2 daily dosing on day 1-14 every 3 weeks; C) daily dosing day
1-5 every 3 weeks to assess safety, pharmacokinetics (PK) and efficacy. 

Results: 
92 patients, median age 59 have been included. Major cancer types included
colorectal (21%), prostate (16%), bladder (11%). Most frequent related adverse
events were fatigue (54%), nausea (52%), anorexia (40%), vomiting (32%),
diarrhea (29%) as we know them from other studies of belinostat. Hematological
toxicity was mild. The patients had in general been treated with prior multiple
lines of therapy median 3 (range 1-11). 

Recommended dose for A) continuous dosing was determined as 250 mg once or
twice daily, recommended dose for B) was determined as 750 mg daily, with
option for intra-pt dose escalation if limited toxicity. For schedule C) the
recommended dose was determined as 2000 mg daily, also here with option for
intra-pt dose escalation if limited toxicity. 

Tumor growth control (SD) has been reached in 48 patients (64% of the 75
evaluable patients) and the duration was 3 months or more in 15 patients for
example 710 days in a patient with adenoid cystic cancer; 510 days in a
patients with bladder cancer and 485 days in a patient with renal cancer. 

Conclusions: 
Oral belinostat can be delivered safely in multiple schedules. Despite a median
of 3 prior lines of therapy 48 (64%) of 75 evaluable patients achieved tumor
growth control (SD), 15 patients had a treatment duration ≥ 3 months. 

The safety profile and long stabilizations in multiple tumor types makes
belinostat an interesting option for further evaluation as a monotherapy and in
combination with chemotherapy. 

Oral belinostat should be further evaluated in disease specific solid tumor
phase II studies. 

TopoTarget A/S

For further information, please contact:

Peter Buhl Jensen	Telephone	+45 39 17 94 99
CEO		Mobile	+45 21 60 89 22