Published: 2012-08-28 11:34:35 CEST
Topotarget
Company Announcement

Further results of the phase II clinical trial with belinostat in cancer of unknown primary (CUP) indicate clinical activity

To NASDAQ OMX Copenhagen A/S
Announcement no. 12-12 / Copenhagen, August 28, 2012

Copenhagen, Denmark – August 28, 2012 – Topotarget A/S (NASDAQ OMX: TOPO) today announced further exploratory analysis for its randomized phase II belinostat trial in patients with CUP.

Following the release of the top-line results on June 29, 2012, Topotarget has further reviewed and analyzed the outcome of the CUP phase II study with support from investigators and members of our Global Oncology Advisory Board.

  • As previously communicated, the study did not meet its primary endpoint of improving the median progression-free survival (PFS), but showed a highly statistically significant increase (43.2% vs. 22.2%; p=0.0252) in objective response rate in the intent-to-treat (ITT) population. In addition, the median overall survival (OS) in the ITT population was 11.5 months for the belinostat and carboplatin/paclitaxel (BelCaP) treated group versus 9.1 months for patients on carboplatin/paclitaxel (CaP), a 2.4 months increase in OS favoring the BelCaP group (hazard ratio (HR)=0.861; p=0.2906, non-significant).
  • Topotarget has carried out additional analyses of the underlying data including a “time to failure (TTF) of treatment” assessment where patients who went on subsequent therapy prior to disease progression were taken into account. Failure of treatment is defined as death, progression of the malignant disease, or addition of new anti-cancer therapy prior to disease progression (whichever came first). The analysis was carried out  as a substantial number of patients (six in all; five patients in the CaP group and one patient in the BelCaP group received new and additional anti-cancer therapy even though a progression had not been documented at the time of adding therapy. This TTF analysis showed an increase in the median duration to failure of treatment of 2.2 months in favor of BelCaP compared to CaP (5.4 months in the BelCaP group versus 3.2 months in the CaP group in the per-protocol (PP) population; HR was 0.892 [0.540-1.473] (p=0.3271, non-significant). Furthermore, the OS in the PP population showed a 30% survival improvement trending towards statistical significance (HR 0.771, p=0.1744).
  • The TTF data as well as the OS results, albeit being not statistically significant, together with the impressive overall response rate (ORR) indicate clinical activity of the BelCaP regimen in the treatment of patients with CUP.

“Taken together, we believe that there are interesting signals of clinical activity when using belinostat in combination with standard chemo regimen (CaP – carboplatin and paclitaxel) in the treatment of solid tumors,” said CEO, Francois Martelet. “Further randomized and sufficiently powered studies in well-defined disease entities such as lung, bladder, and ovarian cancer using belinostat in combination with CaP  chemotherapy regimen may confirm these preliminary clinical signals. In addition, and separate from the CUP study, we, later this year, look forward to the results of our currently on-going pivotal BELIEF study in the hematologic indication of peripheral T-cell lymphoma using single agent belinostat”.


Trial background
The CLN-17 study in CUP was a randomized, controlled, open-label, multinational, comparative efficacy and safety phase II trial  of Topotarget’s compound belinostat in combination with carboplatin and paclitaxel (BelCaP), compared to carboplatin and paclitaxel (CaP), in patients with previously untreated CUP.

The objective of the trial was to provide an estimate of the hazard ratio of treatment effect of BelCaP compared to CaP, with the primary study endpoint being defined as a PFS improvement of at least 60%. Secondary endpoints include overall response rate (ORR), OS, and safety assessment.

The main findings from the study were:

  • The primary efficacy analysis of PFS for BelCaP vs. CaP in the ITT population did not show statistical significance at the 10% level for the stratified, one-sided log-rank test. The p-value was 0.5526 and the median PFS was 5.4 versus 5.3 months. HR = 1.034 [95% confidence interval (CI): 0.631, 1.694]
  • The response rate in the ITT population was 43.2% vs. 22.2%, which is statistically significant. HR = 2.850 [CI: 1.117, 7.272], p-value = 0.0252
  • The median OS in the ITT population was 9.1 on CaP versus 11.5 on BelCaP, a 2.4 months increase in OS favoring the BelCaP group. HR = 0.861 [CI: 0.504, 1.469], p-value = 0.2906, non-significant
  • The median OS in the PP population was 9.1 on CaP versus 11.5 on BelCaP, a 2.4 months increase in OS favoring the BelCaP group. HR = 0.771 [CI: 0.447, 1.330], p-value = 0.1744, non-significant. PP was defined as patient population who received assigned treatment and with post-baseline tumour assessment and no major protocol violation
  • The BelCaP combination was generally well-tolerated during the first six cycles of treatment. This was also the case in the subsequent maintenance period where belinostat was given as oral monotherapy treatment
  • Finally we also evaluated if the histology, the degree of differentiation, or the site of metastasis had any bearing on the doubling of the response rate. The outcome of the read-out indicates that these parameters do not significantly impact the outcome of the primary analysis


Conclusion
The study’s primary endpoint of PFS was not met although there was a highly significant increase in the response rate.

When taking patients who received additional therapy prior to progression of disease into account, the analysis did show a non-significant, but clinically interesting, increase in time to treatment failure in the BelCaP group by >2 months in the PP analysis. The median OS was increased by >2 months in the BelCaP group (not significant).

We conclude that this study provides encouraging signs of clinical efficacy and a favorable safety profile of belinostat when used in combination with carboplatin/paclitaxel.

We are working together with key investigators and expect data to be presented at major international oncology meetings in 2013. We also plan on submitting the study results for peer-review in international oncology journals.

 

Topotarget A/S

For further information, please contact:

Francois Martelet, CEO: Direct: +45 39 17 83 43; Cell: +45 51 32 83 41

Axel Mescheder, CMDO: Direct: +45 39 17 83 14; Cell: +45 51 55 71 66

Anders Vadsholt, CFO: Direct: +45 39 17 83 45; Cell: +45 28 98 90 55

 

Background information

About Topotarget

Topotarget (NASDAQ OMX: TOPO) is an international biopharmaceutical company headquartered in Copenhagen, Denmark, dedicated to clinical development and registration of oncology products. In collaboration with Spectrum Pharmaceuticals, Inc., Topotarget focuses on the development in pivotal studies of its lead drug candidate, belinostat, which has shown positive results as a monotherapy treating hematological malignancies and positive results in solid tumors. Belinostat may be used in combination with full doses of chemotherapy, and is in a pivotal trial within PTCL (peripheral T-cell lymphoma). For more information, please refer to www.topotarget.com.

Topotarget Safe Harbor Statement
This announcement may contain forward-looking statements, including statements about our expectations of the progression of our preclinical and clinical pipeline including the timing for commencement and completion of clinical trials and with respect to cash burn guidance. Such statements are based on management's current expectations and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Topotarget cautions investors that there can be no assurance that actual results or business conditions will not differ materially from those projected or suggested in such forward-looking statements as a result of various factors, including, but not limited to, the following: The risk that any one or more of the drug development programs of Topotarget will not proceed as planned for technical, scientific, or commercial reasons or due to patient enrollment issues or based on new information from non-clinical or clinical studies or from other sources; the success of competing products and technologies; technological uncertainty and product development risks;  uncertainty of additional funding; Topotarget's history of incurring losses and the uncertainty of achieving profitability; Topotarget's stage of development as a biopharmaceutical company; government regulation; patent infringement claims against Topotarget's products, processes, and technologies; the ability to protect Topotarget's patents and proprietary rights; uncertainties relating to commercialization rights; and product liability exposure. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, unless required by law.

 


Announcement no. 12-12 Further results of ph II clinical trial with belinostat in CUP indicate clinical activity.pdf