TopoTarget meddeler flotte safety data for Belinostat i PTCL

Man kan så undre sig lidt over hvorfor de ikke vil give os ORR, PFS eller OS data. Men lad det nu være 🙂

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Til NASDAQ OMX Copenhagen A/S Meddelelse nr. 01-13 / København, 24. januar 2013

Topotarget A/S (NASDAQ OMX: TOPO) meddeler, at der vil blive offentliggjort kliniske data om belinostat på det 5. årlige T-Cell Lymphoma Forum, som afholdes 24.-26. januar 2013 i San Francisco, USA.

I det videnskabelige resumé præsenteres foreløbige sikkerhedsdata fra det pivotale fase II BELIEF-studie (CLN-19) med belinostat som enkeltstofbehandling af patienter med recidiverende og/eller resistent perifert T-celle lymfekræft. Det konkluderes, at belinostat er veltolereret og har en favorabel sikkerhedsprofil i behandlingen af patienter med PTCL, samt at belinostat potentielt kan være et veltolereret alternativ i behandlingen af PTCL. Poster-præsentationen vil blive præsenteret den 26. januar.

Teksten fra det videnskabelige resumé er gengivet nedenfor:

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% respectively^{1, 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.