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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
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
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.
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
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


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 Storys: PharmaMar and Zeltia Group
Weitere Storys: PharmaMar and Zeltia Group
  • 07.04.2005 – 15:30

    YONDELIS(R) Granted Orphan Drug Designation by the U.S. FDA For The Treatment of Ovarian Cancer

    Madrid, Spain (ots/PRNewswire) - PharmaMar announced today that its marine-derived anti-cancer drug, YONDELIS(R) (trabectedin), has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of ovarian cancer. The U.S. application sponsor, is Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), ...