Copenhagen, Denmark - 13 September, 2011 - Today Topotarget A/S (NASDAQ OMX: TOPO.CO) announcedthat clinical data on belinostat will be presented at The European Multidisciplinary Cancer Congress in Stockholm, 23-27 September 2011.
Below is a list of the two abstracts accepted at The European Multidisciplinary Cancer Congress http://stockholm2011.ecco-org.eu/Programme;
Abstract 6597, Monday 26 September, time: 8.00-10.00, Hall C
A phase II study of epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter study of the Mayo Phase 2 Consortium (P2C) and the Cancer Therapeutics Research Group (CTRG)
W. Yeo1, H.C. Chung2, S.L. Chan1, L.Z. Wang,3 R. Lim3, J. Picus4, M. Boyer5, C. Erlichman6, A.T.C. Chan1, B.C. Goh3. Department of Clinical Oncology1, Chinese University of Hong Kong, Hong Kong. Division of Haematology-Onology, Yonsei Cancer Center, Yonsei University College of Medicine, Korea2. Department of Haematology-Oncology, National University Hospital, Singapore3. Washington University, School of Medicine, St. Louis, MO, USA4. Sydney Cancer Centre, Royal Prince Alfred Hospital, Australia5. Mayo Phase 2 Consortium6.
Background: Patients with unresectable hepatocellular carcinoma (HCC) carry a dismal prognosis. Epigenetic aberrations have been reported in HCC. Belinostat is a novel, low molecular weight, histone deacetylase inhibitor. The purpose of this study was to assess the efficacy of epigenetic therapy with belinostat in patients with unresectable HCC.
Patients and methods: Major eligibility criteria included histologically confirmed HCC that is not amenable to curative treatment; ECOG£2; adequate organs functions. The belinostat dose used was 1400 mg/m2/day i.v. on day 1-5 every 3 weeks, as defined in a prior phase I study. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were response rate (RR) according to RECIST and overall survival (OS). Adverse events were reported using CTCAE v3.
Results: 42 patients were accrued. Prior therapies included surgery (36%), radiofrequency ablation (7%), transarterial therapy (50%); prior systemic therapies (38%). Median follow-up was 20.0 months. Median cycle no. was 2 (range: 1-12). The PR and SD rate was 2.4% (1/42) and 45.2% (19/42) respectively. Median PFS was 2.64 months (95%C.I. 1.55-3.17) and OS was 6.60 months (95%C.I. 4.53-11.60). Grade >3 toxicities that occurred in >5% included: 4 (9.5%) abdominal pain, 4 (9.5%) hyperbilirubinemia, 4 (9.5%) raised alanine transaminase, 3 (7.1%) anemia, 3 (7.1%) vomiting, 2 (4.8%) distension, 2 (4.8%) hemorrhage, 2 (4.8%) prolonged QTc and 2 (4.8%) dehydration. One patient developed sudden death but it was determined not likely due to study medication.
Conclusions: With the majority of patients having failed prior therapy, epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. Further studies including combinational study with other agents is warranted.
Acknowledgement: The study was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, U.S.A, and its collaborator TopoTarget.
Abstract 7105, Sunday 25 September, time: 11-12, Hall A8
Belinostat in Combination With Carboplatin and Paclitaxel (BelCaP) for Treatment of Bladder Cancer - a Pharmacokinetic Study of Exposure to Belinostat and Its Metabolites
Co-authors: R.J. Jones1, J. Tjørnelund2, K.D. Erichsen3, L. Sengeløv4, J. De Bono5
1Cancer Research UK Beatson Laboratories, Centre for Oncology and Applied Pharmacology, Glasgow, United Kingdom ; 2Topotarget, Clinical Pharmacology, Copenhagen, Denmark ; 3Topotarget, Medical Affairs, Copenhagen, Denmark ; 4Herlev Hospital, Department Oncology, Copenhagen, Denmark ; 5Royal Marsden Hospital, Institute for Cancer Research, Sutton, United Kingdom
Background: Belinostat (Bel, PXD101) is a class I and II Histone DeACetylase (HDAC) inhibitor. A single arm Ph II study was conducted to evaluate the safety and activity of Belinostat, Carboplatin and Paclitaxel (BelCaP) in patients (pts) with Transitional Cell Carcinoma of the Bladder (TCCB) (n=15). A part of the study was a pharmacokinetic study of plasma exposure to Bel and its metabolites. The in vitro efficacy of belinostat and its metabolites were compared and related to plasma exposure in pts.
Materials and Methods: Pts with TCCB were treated with BelCaP every third week; Bel was given as a 1000mg/m2 30-min i.v. inf. on days 1-5 with P (175mg/m2) and subsequently Ca (AUC5) administered 2-3hrs after Bel on day 3. The plasma exposure (AUC) of Bel and its metabolites were determined. The in vitro pharmacological effect of Bel and its five major metabolites: belinostat glucuronide (BelGlcU), 3-(Anilinosulfonyl)benzene carboxylic acid (3-ASBA), methylated belinostat (Metbel), belinostat amide (Belam) and belinostat acid (Belac) were examined in a HeLa HDAC enzyme inhibition assay (HDAC-i), in WST proliferation assays and in clonogenic assays (CA). Fold differences in exposure of metabolites and belinostat (10 pts on day 3) and fold differences in in vitro efficacy of belinostat and metabolites were compared.
Results: The exposure of each metabolite relative to Bel was evaluated. The increases (molar AUC0-∞) relative to Bel were 16- (BelGlcU), 3- (3-ASBA), 1- (Metbel), 1- (Belam) and 0.5-fold (Belac).
Bel metabolites did not inhibit HDAC-i activity or cell WST proliferation in vitro. In the CAs the IC50 for Bel were 0.4 to 1.3µM. Three metabolites had weak effect relative to Bel. The fold increase in IC50 relative to Bel was: >65 (BelGlcU), >42 (Metbel) and >114 (Belam).
Conclusions: Five major human Bel metabolites (BelGlcU, 3-ASBA, Metbel, Belam and Belac) were identified in a Ph II study of BelCaP in pts with TCCB. Bel metabolites were inactive in HDAC-i assays and in WST assays and had weak activity in CA. The metabolite with highest fold exposure compared to Bel was BelGlcU (16-fold), which was 65 fold less effective in vitro than Bel. The present study finds that Bel metabolites do not have significant biological effect at therapeutic relevant plasma exposure in cancer pts.
Today's news does not change Topotarget's full-year financial guidance for 2011.
Below is a list of the two abstracts accepted at The European Multidisciplinary Cancer Congress http://stockholm2011.ecco-org.eu/Programme;
Abstract 6597, Monday 26 September, time: 8.00-10.00, Hall C
A phase II study of epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter study of the Mayo Phase 2 Consortium (P2C) and the Cancer Therapeutics Research Group (CTRG)
W. Yeo1, H.C. Chung2, S.L. Chan1, L.Z. Wang,3 R. Lim3, J. Picus4, M. Boyer5, C. Erlichman6, A.T.C. Chan1, B.C. Goh3. Department of Clinical Oncology1, Chinese University of Hong Kong, Hong Kong. Division of Haematology-Onology, Yonsei Cancer Center, Yonsei University College of Medicine, Korea2. Department of Haematology-Oncology, National University Hospital, Singapore3. Washington University, School of Medicine, St. Louis, MO, USA4. Sydney Cancer Centre, Royal Prince Alfred Hospital, Australia5. Mayo Phase 2 Consortium6.
Background: Patients with unresectable hepatocellular carcinoma (HCC) carry a dismal prognosis. Epigenetic aberrations have been reported in HCC. Belinostat is a novel, low molecular weight, histone deacetylase inhibitor. The purpose of this study was to assess the efficacy of epigenetic therapy with belinostat in patients with unresectable HCC.
Patients and methods: Major eligibility criteria included histologically confirmed HCC that is not amenable to curative treatment; ECOG£2; adequate organs functions. The belinostat dose used was 1400 mg/m2/day i.v. on day 1-5 every 3 weeks, as defined in a prior phase I study. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were response rate (RR) according to RECIST and overall survival (OS). Adverse events were reported using CTCAE v3.
Results: 42 patients were accrued. Prior therapies included surgery (36%), radiofrequency ablation (7%), transarterial therapy (50%); prior systemic therapies (38%). Median follow-up was 20.0 months. Median cycle no. was 2 (range: 1-12). The PR and SD rate was 2.4% (1/42) and 45.2% (19/42) respectively. Median PFS was 2.64 months (95%C.I. 1.55-3.17) and OS was 6.60 months (95%C.I. 4.53-11.60). Grade >3 toxicities that occurred in >5% included: 4 (9.5%) abdominal pain, 4 (9.5%) hyperbilirubinemia, 4 (9.5%) raised alanine transaminase, 3 (7.1%) anemia, 3 (7.1%) vomiting, 2 (4.8%) distension, 2 (4.8%) hemorrhage, 2 (4.8%) prolonged QTc and 2 (4.8%) dehydration. One patient developed sudden death but it was determined not likely due to study medication.
Conclusions: With the majority of patients having failed prior therapy, epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. Further studies including combinational study with other agents is warranted.
Acknowledgement: The study was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, U.S.A, and its collaborator TopoTarget.
Abstract 7105, Sunday 25 September, time: 11-12, Hall A8
Belinostat in Combination With Carboplatin and Paclitaxel (BelCaP) for Treatment of Bladder Cancer - a Pharmacokinetic Study of Exposure to Belinostat and Its Metabolites
Co-authors: R.J. Jones1, J. Tjørnelund2, K.D. Erichsen3, L. Sengeløv4, J. De Bono5
1Cancer Research UK Beatson Laboratories, Centre for Oncology and Applied Pharmacology, Glasgow, United Kingdom ; 2Topotarget, Clinical Pharmacology, Copenhagen, Denmark ; 3Topotarget, Medical Affairs, Copenhagen, Denmark ; 4Herlev Hospital, Department Oncology, Copenhagen, Denmark ; 5Royal Marsden Hospital, Institute for Cancer Research, Sutton, United Kingdom
Background: Belinostat (Bel, PXD101) is a class I and II Histone DeACetylase (HDAC) inhibitor. A single arm Ph II study was conducted to evaluate the safety and activity of Belinostat, Carboplatin and Paclitaxel (BelCaP) in patients (pts) with Transitional Cell Carcinoma of the Bladder (TCCB) (n=15). A part of the study was a pharmacokinetic study of plasma exposure to Bel and its metabolites. The in vitro efficacy of belinostat and its metabolites were compared and related to plasma exposure in pts.
Materials and Methods: Pts with TCCB were treated with BelCaP every third week; Bel was given as a 1000mg/m2 30-min i.v. inf. on days 1-5 with P (175mg/m2) and subsequently Ca (AUC5) administered 2-3hrs after Bel on day 3. The plasma exposure (AUC) of Bel and its metabolites were determined. The in vitro pharmacological effect of Bel and its five major metabolites: belinostat glucuronide (BelGlcU), 3-(Anilinosulfonyl)benzene carboxylic acid (3-ASBA), methylated belinostat (Metbel), belinostat amide (Belam) and belinostat acid (Belac) were examined in a HeLa HDAC enzyme inhibition assay (HDAC-i), in WST proliferation assays and in clonogenic assays (CA). Fold differences in exposure of metabolites and belinostat (10 pts on day 3) and fold differences in in vitro efficacy of belinostat and metabolites were compared.
Results: The exposure of each metabolite relative to Bel was evaluated. The increases (molar AUC0-∞) relative to Bel were 16- (BelGlcU), 3- (3-ASBA), 1- (Metbel), 1- (Belam) and 0.5-fold (Belac).
Bel metabolites did not inhibit HDAC-i activity or cell WST proliferation in vitro. In the CAs the IC50 for Bel were 0.4 to 1.3µM. Three metabolites had weak effect relative to Bel. The fold increase in IC50 relative to Bel was: >65 (BelGlcU), >42 (Metbel) and >114 (Belam).
Conclusions: Five major human Bel metabolites (BelGlcU, 3-ASBA, Metbel, Belam and Belac) were identified in a Ph II study of BelCaP in pts with TCCB. Bel metabolites were inactive in HDAC-i assays and in WST assays and had weak activity in CA. The metabolite with highest fold exposure compared to Bel was BelGlcU (16-fold), which was 65 fold less effective in vitro than Bel. The present study finds that Bel metabolites do not have significant biological effect at therapeutic relevant plasma exposure in cancer pts.
Today's news does not change Topotarget's full-year financial guidance for 2011.
Idag fick vi ett gyllene köpläge när några få aktörer helt tappade besinningen. Två studier rörande Belinostat, som visserligen var kända redan igår, tillkännagavs idag från bolaget självt. Den första var en fin studie rörande Belinostat i HCC som jag skall återkomma till, men det var den andra studien som skapade viss oro på marknaden för den var lite för svår för en lekman att omedelbart förstå.
Det handlade här om en säkerhetsstudie rörande BelCaP, som också undersöker eventuella bieffekter av Bel. Resultatet är: Inga problem!
Men vissa aktörer begrep inte detta när de läste: "The present study finds that Bel metabolites do not have significant biological effect at therapeutic relevant plasma exposure in cancer pts.". Det var för svårt. Istället läste man: "Bel ... do not have significant biological effect ... in cancer" och drabbades av panik.
I själva verket är det två MYCKET bra resultat som annonseras, där jag själv räknar den aktuella FAS II-studien som otroligt viktig. HCC genererar 600.000 nya fall per år. Ingen bot finns. Dödligheten är mycket snabb och närmast total. Mot detta erbjuder nu Belinostat en stable disease rate på 45.2% (19 av 42 patienter)!
Då skall man veta att en kombinationsbehandling med bortezomib har visat sig kunna kraftigt öka effekten! Se följande länk:
http://ar.iiarjournals.org/content/31/4/1093/F2.expansion.html
HCC-studien har enligt mitt förmenande dramatiskt ökat Belinostats marknadsvärde. Kursen har dock ännu knappt rört sig. Den började visserligen starkt men sänktes av den nämnda idiotreaktionen. Vi borde dock få ett rally innan kvällen.
Det handlade här om en säkerhetsstudie rörande BelCaP, som också undersöker eventuella bieffekter av Bel. Resultatet är: Inga problem!
Men vissa aktörer begrep inte detta när de läste: "The present study finds that Bel metabolites do not have significant biological effect at therapeutic relevant plasma exposure in cancer pts.". Det var för svårt. Istället läste man: "Bel ... do not have significant biological effect ... in cancer" och drabbades av panik.
I själva verket är det två MYCKET bra resultat som annonseras, där jag själv räknar den aktuella FAS II-studien som otroligt viktig. HCC genererar 600.000 nya fall per år. Ingen bot finns. Dödligheten är mycket snabb och närmast total. Mot detta erbjuder nu Belinostat en stable disease rate på 45.2% (19 av 42 patienter)!
Då skall man veta att en kombinationsbehandling med bortezomib har visat sig kunna kraftigt öka effekten! Se följande länk:
http://ar.iiarjournals.org/content/31/4/1093/F2.expansion.html
HCC-studien har enligt mitt förmenande dramatiskt ökat Belinostats marknadsvärde. Kursen har dock ännu knappt rört sig. Den började visserligen starkt men sänktes av den nämnda idiotreaktionen. Vi borde dock få ett rally innan kvällen.
13/9 2011 11:49 turin 0
46311 "gyllene köpläge", Gorm!? Det har vist været "köpläge" siden kurs 5, eller?
- turin
- turin
13/9 2011 13:46 Fiskemanden 146315 Godt set,i dag Gorm !!
Og når du nu har ret så hvorfor ikke bare overse med Turins unødvendige spydigheder ???
Kursen rykker nu endelig så det vil noget,så skal vi ikke bare lade det tale for sig selv. ;0))
Og når du nu har ret så hvorfor ikke bare overse med Turins unødvendige spydigheder ???
Kursen rykker nu endelig så det vil noget,så skal vi ikke bare lade det tale for sig selv. ;0))
14/9 2011 03:11 polopolo 046343 Hej er selv langtidsaktionær i Topo og derfor interesseret .
Men der må være en sprogforbistring her !
Turin har helt ret aktien er faldet og faldet og har derfor kostet aktionærer en masse penge .
Og det ser altså ud til at det er Gorm der bander af andre debattører -Eller har jeg misforstået både det med kursen og forbandelserne?
Hilsen Polopolo
Men der må være en sprogforbistring her !
Turin har helt ret aktien er faldet og faldet og har derfor kostet aktionærer en masse penge .
Og det ser altså ud til at det er Gorm der bander af andre debattører -Eller har jeg misforstået både det med kursen og forbandelserne?
Hilsen Polopolo
13/9 2011 21:07 cyber 046331 Turin, tag dig sammen, du er kun ude på at genere folk, Gorm er alletiders, vi har brug for al den info vi kan få om belinostat, så lad os få arbejdsro. Har du seriøs info, er du selvfølgelig velkommen, men hold dig væk med dine spydigheder..
15/9 2011 09:25 turin 046406 cyber, jeg gentager. Jeg har i årevis været TOPO-aktionær og er det stadig. Jeg har ingen intention om at genere nogen, men bare at få spredt lidt realitetssans.
- turin
- turin
Helt enig med fiskemanden. Du fik ret og du skrev det mens der var panik og minus og se hvad der skete. Bliv endelig ved med at komme med inputs her.
sent from iPhone
sent from iPhone
Mens vi venter på data i CUP ( et studie som er sponsoreret af Topo ), fik vi gode HCC-data, et studie sponsoreret af NCI.
HCC-studiet er lovende, når vi kigger på SD, og en kombination med bortezomib, som Gorm anfører, vil uden tvivl opgradere OS, der med belinostat
mono er 6.60 mdr., og vi snakker om dødsyge patienter med en meget trist prognose.
Jeg har ikke flere indlæg på EI i dag, brugte hurtigt de 30 jeg har, og kan derfor ikke opponere mod birket som påstår, at det er CUP-data vi har fået, intet er mere forkert.
Stigningen vi så i dag, mener jeg, kan tillægges RAJ's optimistiske udtalelser på konferencen i går, hvor han understreger sin tro på BelCaP som Backbone Of Cancer Therapy med CUP og NSCLC som drivkrafterne.
Ydermere sagde RAJ, at indrulningen til PTCL vil slutte hvilken som helst dag, og NDA-en kommer i 2012.
Topo er et meget stærkt køb..
HCC-studiet er lovende, når vi kigger på SD, og en kombination med bortezomib, som Gorm anfører, vil uden tvivl opgradere OS, der med belinostat
mono er 6.60 mdr., og vi snakker om dødsyge patienter med en meget trist prognose.
Jeg har ikke flere indlæg på EI i dag, brugte hurtigt de 30 jeg har, og kan derfor ikke opponere mod birket som påstår, at det er CUP-data vi har fået, intet er mere forkert.
Stigningen vi så i dag, mener jeg, kan tillægges RAJ's optimistiske udtalelser på konferencen i går, hvor han understreger sin tro på BelCaP som Backbone Of Cancer Therapy med CUP og NSCLC som drivkrafterne.
Ydermere sagde RAJ, at indrulningen til PTCL vil slutte hvilken som helst dag, og NDA-en kommer i 2012.
Topo er et meget stærkt køb..
