PharmaMar and Zeltia Group

YONDELIS(TM) (trabectedin) Phase II Trials Demonstrate Activity in Prostate, Ovarian and Breast Cancer

    Orlando, Florida (ots/PRNewswire) -

    - New Results Presented at ASCO

    Results from five clinical studies of YONDELIS (TM) (trabectedin) were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO), in Orlando, Florida, from 13-17 May 2005. YONDELIS is being developed by PharmaMar in partnership with Johnson & Johnson Pharmaceutical Research & Development, L.C.C. (J&JPRD).

    In addition, a poster was presented on a second PharmaMar anti-cancer drug, Kahalalide F.

    YONDELIS presentations

    Results from a Phase II study of a three hour, weekly infusion of YONDELIS (trabectedin) in patients with androgen-independent advanced prostate carcinoma were presented during an oral session (Sunday, 15 May, 11:15 - 11:30 am) by Dr D. Michaelson of the Massachusetts General Hospital Cancer Center in Boston, MA.

    This Phase II trial was designed to test the activity of weekly administration of YONDELIS in patients with hormone refractory prostate cancer with high levels of PSA (prostate specific antigen, a biological marker related to tumor activity).

    The primary objective of the trial was to assess the PSA responses to the treatment, confirmed by decrease of PSA blood levels.

    In this study, 27 patients have been enrolled to date; 19 received YONDELIS as second line chemotherapy (following the approval of Taxotere(R) (docetaxel) in 2004 by the U.S. Food and Drug Administration (FDA) as standard front-line chemotherapy for androgen-independent prostate cancer); eight patients received YONDELIS as a first line therapy. Fourteen of the patients enrolled were refractory to docetaxel-based chemotherapy.

    The preliminary results demonstrated an overall PSA response rate in the docetaxel refractory population of about 14% (two out of 14 patients). Another PSA response was observed in a chemotherapy naïve patient. An additional three men have demonstrated an initial PSA decline that will be assessed in subsequent evaluations as they are still receiving treatment. To date, the overall PSA response rate is 12% (3/26 evaluable patients including one chemotherapy naïve patient). A symptomatic improvement, with an average sustained PSA response of 23 weeks, was observed in all the PSA responders.

    The preliminary safety results indicate good tolerance of weekly administration: no patients presented grade 4 adverse events. The most frequent adverse events were fatigue, nausea and anaemia; only five patients experienced grade 3 fatigue.

    The activity observed in this study, including activity in patients refractory to taxotere (docetaxel), is encouraging for the further evaluation of YONDELIS in patients with prostrate cancer.

    "This is encouraging data," said Dr. Michaelson. "The results from this study suggest that YONDELIS is effective in reducing PSA and alleviating pain in approximately 12% of men with advanced prostate cancer. Most encouraging is that YONDELIS appears to have the same level of activity in men who are refractory to standard chemotherapy with docetaxel, for whom there is currently no established effective treatment. Thus, YONDELIS should be studied further in this setting, and may bring new hope to men with advanced prostate cancer."

    An additional cohort of patients will now be recruited to expand the study of YONDELIS in prostate cancer.

    Poster: "Final results of Phase II study of weekly trabectedin in second-line and third-line ovarian carcinoma," presented in Gynaecologic Cancer session (Saturday 14 May, 1:00-4:00pm) by Dr. S. McMeekin, University of Oklahoma Health Science Center.

    The final results of a Phase II study of weekly YONDELIS (trabectedin) administration in second/third line ovarian carcinoma were presented.

    The study in pre-treated patients with advanced ovarian cancer featured a weekly dosing schedule using a 0.58 mg/m2 infusion. In the platinum sensitive group (treatment free interval of 6 months or greater) 55 patients were treated; the response rate was 28.8% and the median PFS was 5.1 months. In the platinum resistant group (treatment free interval of less than 6 months) 64 patients were treated; the response rate was 4.8% and the median PFS was 2.0 months. Grade 3-4 toxicities in pooled cycles were reversible liver ALT (alanine aminotransferase) elevation (12%), neutropenia (8%), fatigue (5%), and nausea/vomiting (4%).

    The conclusions of this study are that YONDELIS is active and well tolerated when administered as a 3-hour infusion for three weeks out of a four-week cycle in platinum sensitive patients.

    This is the second study where YONDELIS has shown activity in second line ovarian cancer. The activity with this dose and schedule of YONDELIS is comparable to that reported for alternative agents used in second line therapy after platinum therapy.

    Poster: "Final results of a combination study between trabectedin and pegylated liposomal doxorubicin (PLD) in patients with advanced malignancies," presented in Developmental Therapeutics: Molecular Therapeutics session (Sunday 15 May, 8:00-12:00pm) by Dr R. Cohen from Fox Chase Cancer Center.

    The final results of a combination study on YONDELIS (trabectedin) and Pegylated Liposomal Doxorubicin (PLD) in patients with advanced malignancies (Phase I) were presented.

    A Phase I trial of 30 heavily pre-treated patients was conducted to study the combination of YONDELIS and PLD, known as CAELYX(R) in Europe, and DOXIL(R) (doxorubicin HCI liposome injection) in the US. The recommended dose of YONDELIS combined with 30 mg/m2 PLD every three weeks is 1.1 mg/m2 every 21 days. The combination was well tolerated, and of the 30 patients included, six had a partial response (2 sarcomas, 1 head & neck tumor, 1 peritoneal adenocarcinoma, 1 vaginal adenocarcinoma and 1 neuroectodermal tumor) and 14 had stable disease for more than three months.

    YONDELIS has demonstrated activity in second line in ovarian cancer as previously published. This study demonstrates the combination of YONDELIS with PLD is well tolerated when administered at near full therapeutic doses for prolonged periods of time. A Phase III pivotal study in ovarian cancer comparing the combination of YONDELIS plus DOXIL to DOXIL alone is ongoing to demonstrate that YONDELIS plus DOXIL is superior to DOXIL as a single agent, in second line in the treatment of patients with ovarian cancer.

    Poster: "Tumor control and objective responses: single-centre experience with ecteinascidin-743 (ET-743, Yondelis), an active compound for the treatment of patients with advanced soft tissue and bone sarcomas." presented in Sarcoma session (Sunday 15 May, 1:00-5:00pm) by Dr P. Schöffski et al from University Hospital Gasthuisberg, Leuven (Belgium).

    This poster summarised data on YONDELIS (trabectedin), in the treatment of patients with advanced soft tissue and bone sarcomas.

    A retrospective analysis was performed of data from a single-centre of patients who received YONDELIS in a named-patient compassionate use program sponsored by PharmaMar. A total of 89 patients were treated with YONDELIS given as a 24h infusion every three weeks.

    This analysis concluded that YONDELIS induced long-lasting responses and tumor control in a clinically relevant proportion of heavily pre-treated sarcoma patients (RR: 6.7%; clinical benefit at three and six months was 43% and 25% respectively; median duration of response: 9.8 months), with acceptable toxicity.

    Poster: "Trabectedin in third line breast cancer: A multicenter, randomized, Phase II study comparing two administration regimens." will be presented in the Breast Cancer poster session today from 2:00 to 6:00pm by Dr J. Gurtler et al from Fox Chase Cancer Center.

    This poster will discuss data regarding YONDELIS (trabectedin) in third line breast cancer treatment. Patients with advanced breast cancer previously treated with both anthracyclines and taxanes were randomized in a multicenter Phase II study to receive YONDELIS either weekly or every 3 weeks.

    Dr Miguel Angel Izquierdo, Director of Clinical Development at PharmaMar, said: "PharmaMar and J&JPRD are committed to developing YONDELIS based on encouraging available clinical data. The companies believe that YONDELIS may have a place in the therapeutic armamentarium to provide benefit to patients suffering from incurable cancers, thus fulfilling an unmet medical need in many clinical situations."

    Kahalalide F presentation

    Poster: "Clinical and pharmacokinetic Phase I dose-finding study of Kahalalide F (KF) administered as a prolonged infusion in patients with solid tumors." presented in Developmental Therapeutics: Cytotoxic Chemotherapy session (Sunday, 15 May, 8:00 - 12:00pm ) by Dr R. Salazar et al from the Catalan Institute of Oncology, Barcelona (Spain).

    This poster presented the data of a Phase I trial of Kahalalide F in patients with solid tumors.

    The primary endpoint of the study was to identify the recommended dose and to determine safety, toxicity profile and Dose Limiting Toxicities (DLT) for Kahalalide F when administered weekly as a 3 h or a 24 h infusion. Secondary objectives were to study Kahalalide F pharmacokinetics and to document anti-tumor activity.

    The results of the three hour arm were presented in this poster. Overall, most toxicities were mild to moderate (G1-2). Grade 3-4 was only reached by hypersensitivity and laboratory abnormalities. The asymptomatic and reversible increases in transaminases constituted the DLT for the schedule.

    The recommended dose for Phase II for the three hour schedule was 1 mg/m2 per week.

    A Complete Response (CR) was reported in a patient with melanoma and Stable Disease (SD) lasting for >3 months was seen in lung (NSCLC), colon and unknown origin adenocarcinoma patients. These findings suggest potential targets for Phase II evaluation of Kahalalide F given as weekly 3 h infusions.

    The conclusion of the study was that Kahalalide F may be administered safely as a weekly 3-hour intravenous infusion at a dose of 1000 mg/m squared. Future Phase II studies in patients with solid tumors are warranted.

    About YONDELIS(TM)

    YONDELIS (trabectedin), is PharmaMar's most advanced compound in development. It was originally isolated from the marine tunicate Ecteinascidia turbinata, but now is manufactured by chemical synthesis. YONDELIS is being developed by PharmaMar in partnership with Johnson & Johnson Pharmaceutical Research & Development, L.L.C. If key studies are successful and support marketing approval, PharmaMar will market YONDELIS in Europe (including Eastern Europe) while Tibotec Therapeutics, a division of Ortho Biotech Products, L.P., will market it in the U.S., Ortho Biotech, a division of Janssen-Cilag, will market it in the rest of the world.

    Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Ortho Biotech Products, L.P. and Tibotec Therapeutics all are part of the Johnson & Johnson Family of Companies, the world's most comprehensive and broadly based manufacturer of health care products.

    YONDELIS is currently under study in a Phase III pivotal trial in ovarian cancer, and is also being evaluated in Phase II in soft tissue sarcoma (a comparative pivotal trial) and for prostate cancer.

    In clinical studies to date, YONDELIS has shown a good safety and tolerability profile. The most frequent side effect is neutropenia, which is reversible and controllable. A transient increase in transaminases also has been observed.

    YONDELIS is a new chemical entity with unique multicomponent mechanism of action. It is the only chemotherapy agent that binds to the DNA's minor groove and bends toward the major groove, producing its therapeutic effect by interfering with various cell division processes.

    DOXIL(R) (doxorubicin HCl liposome injection) is marketed in the United States by Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., and in Israel by Janssen-Cilag. Schering-Plough Corporation, under a licensing agreement, has exclusive rights to market this medication as CAELYX(R) throughout the rest of the world, excluding Japan.

    About Kahalalide F

    Kahalalide F is a depsipeptide, a novel marine-derived anti-tumour agent isolated from the sea slug Elysia rufescens.

    Kahalalide F alters the function of the lysosomal membrane, a mechanism that distinguishes it from all other known anti-tumour agents. Other mechanisms of action are inhibition of the TGF-alpha expression, blockade of intracellular signalling pathways downstream of EGF and ErbB2 receptor family and induction of non-p53 mediated apoptosis. Studies demonstrate that Kahalalide F induces cell necrosis in vivo (oncosis) and shows selectivity for tumor compared with normal cells in vitro. Its activity is independent of multidrug resistance (MDR) expression.

    Kahalalide F is currently undergoing Phase II clinical trials in various solid tumours: melanoma, non-small cell lung cancer and hepatocellular carcinoma. A Phase II trial for the treatment of patients with severe psoriasis is also ongoing.

    About PharmaMar

    PharmaMar is the world's leading biopharmaceutical companies in advancing cancer care through the discovery and development of innovative marine-derived medicines. PharmaMar's clinical portfolio currently includes: YONDELISTM (co-developed with Johnson & Johnson Pharmaceutical Research & Development) in Phase III clinical trials; it is also designated Orphan Drug for Soft Tissue Sarcomas by the European Commission (E.C.) in 2001 and by the FDA in 2004, and Orphan Drug for ovarian cancer by the E.C. in 2003 and by the FDA in 2005. It also features Aplidin(R), in Phase II, designated Orphan Drug for acute lymphoblastic leukaemia by the E.C. in 2003 and by the FDA in 2004, and for multiple myeloma by the FDA and the EC in 2004; as well as Kahalalide F in Phase II, and ES-285 and Zalypsis(R) in Phase I clinical trials.

    PharmaMar, based in Madrid, Spain, is a subsidiary of the Zeltia Group (Spanish stock exchange, ZEL).

    This press release is also available in the News section on PharmaMar's web site:

    For more information, contact:

    Media: Lola Casals, PharmaMar Communication, tel.: +34-91-846-6000. Coro Egaña, Zeltia Corporate Communication, tel.: +34-91-444-4500. Investors: Catherine Moukheibir, Zeltia Capital Markets Operations,tel.: +34-91-444-4500

ots Originaltext: PharmaMar and Zeltia Group
Im Internet recherchierbar:

Media: Lola Casals, PharmaMar Communication, tel.: +34-91-846-6000.
Coro Egaña, Zeltia Corporate Communication, tel.: +34-91-444-4500.
Investors: Catherine Moukheibir, Zeltia Capital Markets
Operations,tel.: +34-91-444-4500

Weitere Meldungen: PharmaMar and Zeltia Group

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