Spectrum Pharmaceuticals and Onxeo announce complete response in 67% of patients with peripheral T-cell lymphoma in combination of belinostat (Beleodaq®) and standard CHOP // DANISH TRANSLATION: Onxeo og Spectrum Pharmaceuticals offentliggør, at der er opnået komplet respons hos 67 % af patienterne med perifert T-celle lymfekræft (PTCL) med kombinationen af belinostat (Beleodaq®) og standard CHOP-behandling

  • Data was Highlighted in an Oral Presentation of a Phase 1 Study at the 57th Annual Meeting of the American Society of Hematology (ASH)
  • Study Shows 86% Objective Response Rate with 67% Complete Responses in Newly Diagnosed Patients with Peripheral T-cell Lymphoma (PTCL)
  • At Full Dose Intensity the Belinostat-CHOP Combination was Well-Tolerated

HENDERSON, Nev. and PARIS (France), COPENHAGEN (Denmark) – Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations and a primary focus in Hematology and Oncology, and Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), an innovative company specializing in the development of orphan oncology drugs, today jointly announced the results from their Phase 1 combination trial of belinostat (Beleodaq®) with the CHOP (Cyclophosphamide, Hydroxyl-doxorubicin; Vincristine, and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Beleodaq® is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory PTCL in July 2014.

The results were presented today in an oral presentation at the 57th American Society of Hematology (ASH) Annual Meeting & Exposition by Dr. Patrick Johnston, MD, PhD, Assistant Professor of Medicine at the Mayo Clinic, Rochester, MN, USA.

Abstract #253: Safe and Effective Treatment of Patients with Peripheral T-cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial

This open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in Part A, the dose-escalation phase, to determine the study’s primary endpoint, the maximum tolerated dose (MTD).  Part B of the study, the Expansion Phase, enrolled 12 additional patients at this dose level. The MTD of belinostat was established at 1,000 mg/m2 IV infusion on Days 1-5 (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose.  Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: Complete Response + Partial Response), and pharmacokinetics.

Results outlined in the oral presentation showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a Complete Response (14/21), and 19% achieving a Partial Response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) Grade 3-4 hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No Grade 3-4 non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study.

Dr. Patrick Johnston, MD, PhD, Assistant Professor of Medicine at the Mayo Clinic and investigator on the trial, commented, “PTCL is a very difficult lymphoma to treat due to its heterogeneous nature, and its association with multiple recurrence and poor prognosis; only approximately 37% of patients achieve 5-year overall survival. New combination treatment strategies are undeniably needed to improve efficacy without compromising tolerability, and we are encouraged by these Phase 1 study results indicating that the combination of belinostat and CHOP is a potentially viable treatment option. A good safety profile combined with an Objective Response Rate of 86%, and 67% of patients achieving complete response, are unusual in an early trial of this cancer type. We look forward to further evaluating the combination in a planned Phase 3 trial.”

“We are proud to have had several presentations on our products at the ASH meeting, and are optimistic about the new combination data with belinostat,” said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. “Beleodaq was approved for the treatment of patients with relapsed or refractory PTCL based on an Objective Response Rate in the pivotal Phase 2 BELIEF study of 25.8%. The results of this Phase 1 study indicate encouraging safety and efficacy for the combination of belinostat and CHOP in newly diagnosed patients. The clinical activity suggests that earlier treatment with belinostat could be beneficial for the treatment of this devastating disease. Spectrum has a unique PTCL franchise with two FDA approved drugs; we are very proud to be able to offer patients and clinicians additional treatment options for a disease which had no FDA-approved treatments until a few years ago.”

Graham Dixon, PhD, Chief Scientific Officer of Onxeo, added, “We are very excited to have these results discussed in an oral presentation at the ASH Annual Meeting. Collectively, the efficacy and safety findings demonstrate the potential value of belinostat plus CHOP, and Onxeo is thrilled to continue the development of belinostat to more broadly assess this promising therapy in PTCL and beyond.”

References

1. Johnston, P. “Safe and Effective Treatment of Patients with Peripheral T-cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the BelCHOP Phase 1 Trial.” Abstract #253 accepted for Oral Presentation at the 2015 ASH Annual Meeting, Dec. 5-8, 2015. Abstract available online at: https://ash.confex.com/ash/2015/webprogram/Paper83281.html

151206EN_Beleodaq ASH Oral

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DANISH TRANSLATION:

  • Data blev fremhævet i en mundtlig præsentation af et fase I-studie på det 57. årsmøde i American Society of Hematology (ASH)
  • Studiet viser en objektiv responsrate på 86 %, og at 67 % af nyligt diagnosticerede patienter med perifert T-celle lymfekræft (PTCL) opnåede et komplet respons
  • Ved fuld dosisintensitet var belinostat-CHOP kombinationen veltolereret

PARIS (Frankrig), KØBENHAVN (Danmark) og HENDERSON, Nevada (USA) – Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), et innovativt selskab med speciale i udvikling af lægemidler til behandling af sjældne kræftsygdomme, og Spectrum Pharmaceuticals (NasdaqGS: SPPI), et biotekselskab med fuldt integrerede kommercielle aktiviteter og lægemiddeludvikling med hovedvægten på onkologi og hæmatologi, har i dag i fællesskab offentliggjort resultater fra deres fase I-kombinationsstudie med belinostat (Beleodaq®) og kemoterapi-behandlingen CHOP (Cyclophosphamid, Hydroxyl-doxorubicin, Vincristin og Prednisolon) som førstelinjebehandling af nyligt diagnosticeret perifert T-celle lymfekræft (PTCL). Beleodaq® er en histondeacetylase (HDAC)-hæmmer, som af de amerikanske sundhedsmyndigheder (FDA) fik tildelt fremskyndet godkendelse til behandling af PTCL i juli 2014.

Resultaterne blev i dag fremlagt ved en mundtlig præsentation på det 57. årsmøde og udstilling i American Society of Hematology (ASH) af Dr. Patrick Johnston, MD, PhD, Assistant Professor of Medicine på Mayo Clinic, Rochester, MN, USA.

Abstract #253: Sikker og effektiv behandling af patienter med perifert T-celle lymfekræft (PTCL) med den nye HDAC-hæmmer, belinostat, i kombination med CHOP: Resultater af fase I-studiet med Bel-CHOP

I dette ikke-blindede studie i to dele blev der inkluderet i alt 23 patienter. Der blev inkluderet 11 i dosiseskaleringsfasen, Del A, for at fastlægge studiets primære effektmål, maksimalt tålt dosis (MTD). I studiets ekspansionsfase, Del B, blev der inkluderet yderligere 12 patienter på det fastlagte MTD. MTD for belinostat var 1.000 mg/m2, givet som intravenøs infusion på dag 1-5 (den anbefalede enkeltstofdosis), i kombination med CHOP-behandlingen hvor alle stoffer blev givet i den anbefalede dosis. De sekundære effektmål omfattede sikkerhed, tolerabilitet, objektiv responsrate (ORR: komplet respons + partielt respons) og farmakokinetik.

Resultaterne, som blev fremlagt under den mundtlige præsentation, viste en objektiv responsrate på 86 % for kombinationen af belinostat og CHOP baseret på 21 evaluérbare patienter (18/21), hvor langt størstedelen, 67 %, opnåede et komplet respons (14/21), mens 19 % opnåede et partielt respons (4/21). Det sås endvidere, at belinostat-CHOP kombinationsbehandlingen havde en acceptabel bivirkningsprofil uden uventet toksicitet. De hyppigst forekommende (> 10 %) hæmatologiske bivirkninger af grad 3-4, som blev rapporteret med Bel-CHOP, var som forventet: Et reduceret antal neutrocytter (30 %), anæmi (22 %), neutropeni (22 %), et reduceret antal hvide blodlegemer (22 %), febril neutropeni (17 %) og et faldende lymfocyttal (17 %). Der blev ikke rapporteret grad 3-4 non-hæmatologiske bivirkninger i >10 % af patienterne. Der var ingen patienter, som ophørte med behandlingen på grund af bivirkninger. Én patient døde som følge af sygdomsprogression under studiet.

Dr. Patrick Johnston, MD, PhD, Assistant Professor of Medicine på Mayo Clinic og investigator i studiet, udtaler: “PTCL er en meget kompliceret form for lymfekræft at behandle som følge af dens heterogene karakter, og den indebærer hyppige tilbagefald og en dårlig prognose. Således overlever kun ca. 37 % af patienterne fem år. Der er uden tvivl behov for nye kombinationsbehandlinger for at øge behandlingseffekten uden at sætte tolerabiliteten over styr, og vi er opmuntrede af disse fase I-resultater, som indikerer, at kombinationen af belinostat og CHOP er et potentielt brugbart behandlingsvalg. En god sikkerhedsprofil og en samlet responsrate på 86 %, hvor 67 % af patienterne opnåede et komplet respons, er usædvanligt i et tidligt studie denne kræftform. Vi ser frem til yderligere at evaluere kombinationen i et planlagt fase III-studie.”

“Vi er stolte af at have givet flere præsentationer om vores produkter på årsmødet i ASH, og vi er optimistiske omkring de nye kombinationsdata for belinostat,” udtaler Rajesh C. Shrotriya, MD, bestyrelsesformand og administrerende direktør for Spectrum Pharmaceuticals. “Beleodaq er godkendt som behandling af patienter med recidiverende eller resistent PTCL på baggrund af en objektiv responsrate på 25,8 % i det pivotale fase II BELIEF-studie. Resultaterne af dette fase I-studie indikerer en god sikkerhed og effekt af kombinationen af belinostat og CHOP i nyligt diagnosticerede patienter. Den kliniske aktivitet tyder på, at tidligere behandling med belinostat kunne være gavnligt for behandlingen af denne alvorlige sygdom. Spectrum har en unik position med hensyn til behandling af PTCL med to lægemidler, som er godkendt af FDA, og vi er stolte af at kunne tilbyde patienter og læger flere behandlingsvalg til en sygdom, hvor der indtil for nogle få år siden ikke var nogen behandling, der var godkendt af FDA.”

Graham Dixon, PhD, forskningsdirektør hos Onxeo, tilføjer: “Vi glæder os meget over gennemgangen af disse resultater ved en mundtlig præsentation på årsmødet i ASH. Samlet understreger effekt- og bivirkningsresultaterne den potentielle værdi af belinostat plus CHOP, og Onxeo ser frem til at videreudvikle belinostat, så man mere indgående kan vurdere denne lovende behandling både i PTCL og andre indikationer.”

Referencer

1. Johnston, P. “Safe and Effective Treatment of Patients with Peripheral T-cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the BelCHOP Phase 1 Trial.” Abstract #253 accepted for Oral Presentation at the 2015 ASH Annual Meeting, Dec. 5-8, 2015. Abstracts kan ses online på https://ash.confex.com/ash/2015/webprogram/Paper83281.html

151206DK_Beleodaq ASH Oral