COPENHAGEN, Denmark I January 24, 2013 I Topotarget A/S (NASDAQ OMX: TOPO) announces that clinical data on belinostat are presented at the 5th Annual T-Cell Lymphoma Forum on January 24-26, 2013, in San Francisco, USA.
The abstract presents the preliminary safety data from the pivotal phase II BELIEF trial (CLN-19) of belinostat as a single agent in patients with relapsed and/or refractory peripheral T-cell lymphoma (PTCL). It is concluded that belinostat is well-tolerated with a favorable safety profile in patients with PTCL and that belinostat is a candidate for a well-tolerated alternative for the treatment of this disease. The poster is scheduled to be presented at the conference on January 26, 2013.
The abstract text is shown below:
Belinostat in relapsed and/or refractory peripheral T-cell lymphoma (R/R PTCL): Preliminary safety results
Authors: Owen O’Connor, Steve Horwitz, Tamas Masazi, Lauren Pinter-Brown, Shanta Chawla, Andrei Shustov
Background: The prognosis for patients with R/R PTCL remains poor. Romidepsin and pralatrexate are approved in the US; with overall response rates (ORR) of 25% and 27% respectively1, 2. Pralatrexate, an anti folate, causes myelosuppression and mucositis. Fatigue was prominent with romidepsin, an HDACi. This class has been implicated in QTc prolongation. Belinostat, a novel pan-HDACi, in preliminary study has similar ORR in R/R PTCL and is well tolerated with common grade 1-2 toxicities, gastrointestinal and constitutional3. These toxicities were not attenuated in combination studies4. BELIEF is the pivotal Ph 2 study that evaluated the safety and efficacy of belinostat in R/R PTCL. We present the preliminary safety data from the BELIEF study.
Methods: BELIEF is an open-label, multicenter, single-arm efficacy and safety study in patients with R/R PTCL after failure of at least one prior systemic therapy. PTCL diagnosis was confirmed by central pathology review. EKGs were centrally reviewed. Major inclusion criteria were: platelet counts ≥ 50,000/µL, no prior HDACi therapy, measurable disease and adequate organ function. Belinostat was given as a 30 min IV infusion at 1000 mg/m2 on days 1–5 of a 3 week cycle until disease progression or unacceptable toxicity. The primary endpoint was ORR. Safety was monitored through 30 days from the last dose of belinostat. Efficacy determinations are ongoing.
Results: Total of 129 patients, 53% men, median age 63 yr (range 29–81 yr) were treated. The median number of cycles was 2 (range 1–31). One dose reduction occurred in 11% of patients and 1% had two dose reductions. AEs resulted in dose delays in 21% of patients, and 18% discontinued for AEs, including death. Grade 3/4 non hematologic AEs observed in >3% of patients included asthenia/fatigue 9%, pneumonia 7%, dyspnea 6%, infection 4%, febrile neutropenia 4%, pruritus 3%, deep vein thrombosis 3%, and hypotension 3%. Grade 3 QTc prolongation was reported in 2% of patients. Grade 3/4 hematologic toxicities were: thrombocytopenia 6% in patients with platelet counts of ≥100,000, anemia, leukopenia and neutropenia each 13%. A total of 23 patients (18%) died on treatment or within 30 days of last dose, predominantly due to PTCL progression. No death was attributed to belinostat.
Conclusions: Belinostat is well tolerated with a favorable safety profile in patients with R/R PTCL. Based on efficacy in the earlier Ph 2 study and safety in the BELIEF trial, belinostat is a putative well-tolerated option for the treatment of PTCL. Other studies show that full doses of belinostat can be combined with other cytotoxic regimens making combination therapy for patients with PTCL feasible.
Topotarget A/S
For further information, please contact:
Anders Vadsholt, CEO: Direct: +45 39178345
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 of its lead drug candidate, belinostat, which has shown positive results in the treatment of hematological malignancies and solid tumors, obtained by both mono- and combination therapy. For more information, please refer to www.topotarget.com.
About belinostat
Belinostat is a novel pan-HDAC inhibitor in late-stage clinical development with more than 1,000 patients treated. Belinostat has a promising safety profile which allows combination with traditional chemotherapy. Preclinical experiments demonstrated belinostat to be effective against multiple cancers by inhibiting cell proliferation and inducing programed cell death (apoptosis) in tumor cells. Belinostat has been tested in a number of phase I/II clinical trials in hematological cancers and solid tumors both in mono- and combination therapy. Data from these trials have provided evidence of the anti-tumor effect of belinostat, including as monotherapy in PTCL and cutaneous T-cell lymphoma (CTCL), liver cancer, and thymoma.
About the BELIEF trial
BELIEF is a pivotal, open-label, multi-center, single-arm efficacy and safety trial of i.v. belinostat in patients with relapsed or refractory PTCL. FDA has granted belinostat Orphan Drug and Fast Track designation for the treatment of PTCL. The trial was initiated in December 2008 and recruitment was completed with 129 patients in September 2011. In total, the study included approximately 100 clinical centers globally.
SOURCE: Topotarget
Post Views: 104
COPENHAGEN, Denmark I January 24, 2013 I Topotarget A/S (NASDAQ OMX: TOPO) announces that clinical data on belinostat are presented at the 5th Annual T-Cell Lymphoma Forum on January 24-26, 2013, in San Francisco, USA.
The abstract presents the preliminary safety data from the pivotal phase II BELIEF trial (CLN-19) of belinostat as a single agent in patients with relapsed and/or refractory peripheral T-cell lymphoma (PTCL). It is concluded that belinostat is well-tolerated with a favorable safety profile in patients with PTCL and that belinostat is a candidate for a well-tolerated alternative for the treatment of this disease. The poster is scheduled to be presented at the conference on January 26, 2013.
The abstract text is shown below:
Belinostat in relapsed and/or refractory peripheral T-cell lymphoma (R/R PTCL): Preliminary safety results
Authors: Owen O’Connor, Steve Horwitz, Tamas Masazi, Lauren Pinter-Brown, Shanta Chawla, Andrei Shustov
Background: The prognosis for patients with R/R PTCL remains poor. Romidepsin and pralatrexate are approved in the US; with overall response rates (ORR) of 25% and 27% respectively1, 2. Pralatrexate, an anti folate, causes myelosuppression and mucositis. Fatigue was prominent with romidepsin, an HDACi. This class has been implicated in QTc prolongation. Belinostat, a novel pan-HDACi, in preliminary study has similar ORR in R/R PTCL and is well tolerated with common grade 1-2 toxicities, gastrointestinal and constitutional3. These toxicities were not attenuated in combination studies4. BELIEF is the pivotal Ph 2 study that evaluated the safety and efficacy of belinostat in R/R PTCL. We present the preliminary safety data from the BELIEF study.
Methods: BELIEF is an open-label, multicenter, single-arm efficacy and safety study in patients with R/R PTCL after failure of at least one prior systemic therapy. PTCL diagnosis was confirmed by central pathology review. EKGs were centrally reviewed. Major inclusion criteria were: platelet counts ≥ 50,000/µL, no prior HDACi therapy, measurable disease and adequate organ function. Belinostat was given as a 30 min IV infusion at 1000 mg/m2 on days 1–5 of a 3 week cycle until disease progression or unacceptable toxicity. The primary endpoint was ORR. Safety was monitored through 30 days from the last dose of belinostat. Efficacy determinations are ongoing.
Results: Total of 129 patients, 53% men, median age 63 yr (range 29–81 yr) were treated. The median number of cycles was 2 (range 1–31). One dose reduction occurred in 11% of patients and 1% had two dose reductions. AEs resulted in dose delays in 21% of patients, and 18% discontinued for AEs, including death. Grade 3/4 non hematologic AEs observed in >3% of patients included asthenia/fatigue 9%, pneumonia 7%, dyspnea 6%, infection 4%, febrile neutropenia 4%, pruritus 3%, deep vein thrombosis 3%, and hypotension 3%. Grade 3 QTc prolongation was reported in 2% of patients. Grade 3/4 hematologic toxicities were: thrombocytopenia 6% in patients with platelet counts of ≥100,000, anemia, leukopenia and neutropenia each 13%. A total of 23 patients (18%) died on treatment or within 30 days of last dose, predominantly due to PTCL progression. No death was attributed to belinostat.
Conclusions: Belinostat is well tolerated with a favorable safety profile in patients with R/R PTCL. Based on efficacy in the earlier Ph 2 study and safety in the BELIEF trial, belinostat is a putative well-tolerated option for the treatment of PTCL. Other studies show that full doses of belinostat can be combined with other cytotoxic regimens making combination therapy for patients with PTCL feasible.
Topotarget A/S
For further information, please contact:
Anders Vadsholt, CEO: Direct: +45 39178345
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 of its lead drug candidate, belinostat, which has shown positive results in the treatment of hematological malignancies and solid tumors, obtained by both mono- and combination therapy. For more information, please refer to www.topotarget.com.
About belinostat
Belinostat is a novel pan-HDAC inhibitor in late-stage clinical development with more than 1,000 patients treated. Belinostat has a promising safety profile which allows combination with traditional chemotherapy. Preclinical experiments demonstrated belinostat to be effective against multiple cancers by inhibiting cell proliferation and inducing programed cell death (apoptosis) in tumor cells. Belinostat has been tested in a number of phase I/II clinical trials in hematological cancers and solid tumors both in mono- and combination therapy. Data from these trials have provided evidence of the anti-tumor effect of belinostat, including as monotherapy in PTCL and cutaneous T-cell lymphoma (CTCL), liver cancer, and thymoma.
About the BELIEF trial
BELIEF is a pivotal, open-label, multi-center, single-arm efficacy and safety trial of i.v. belinostat in patients with relapsed or refractory PTCL. FDA has granted belinostat Orphan Drug and Fast Track designation for the treatment of PTCL. The trial was initiated in December 2008 and recruitment was completed with 129 patients in September 2011. In total, the study included approximately 100 clinical centers globally.
SOURCE: Topotarget
Post Views: 104
