PharmaMar S.A. Reports New Data On Kahalalide-F And Aplidin(R) At ESMO Congress
Data will also be presented on PharmaMar’s lead cancer compound, YondelisÒ, which demonstrate its potential in combination with carboplatin and expand its potential range of use.
The results of three Phase II trials to evaluate the anti-tumour activity of Kahalalide F will be presented. In all these trials Kahalalide F was administered to patients in a weekly one hour intravenous infusion at a dose of 650 µg/m2. The summary of the data is as follows:
The Phase II clinical trial of Kahalalide F as a second line therapy in patients with advanced non-small cell lung cancer (NSCLC) was a multi-centre, non-randomised study in 31 patients. One partial response was observed and stable disease was reported in eight patients, with the majority of the clinical benefit being seen in patients with squamous cell carcinoma.
The Phase II study of Kahalalide F as a first line therapy in patients with hepatocarcinoma (HC) was a non-randomised study in 22 patients with metastatic or irresectable HC. Stable disease was reported in ten patients (seven lasting more than three months and four lasting more than six months). A 50% decrease in the tumor marker alpha-fetoprotein, AFP (considered to be an indicator of improvement) was observed in two patients.
The Phase II study of Kahalalide F in patients with advanced malignant melanoma (AMM) enrolled 24 patients. Stable disease lasting more than three months was reported in five patients.
In all these trials Kahalalide F was very well tolerated with no serious adverse events reported, showing an excellent tolerability profile.
Aplidin This exploratory Phase II trial of AplidinÒ in patients with advanced renal or colorectal cancer was a multi-centre, open-label, randomised clinical and pharmacokinetic study of AplidinÒ, either alone or in combination with L-carnitine, in patients with advanced renal or colorectal cancer in objective progression. 81 patients were enrolled into two arms of the study, Arm A being administered AplidinÒ at a dose of 5 mg/m2 and Arm B at a dose of 7 mg/m2 plus L-carnitine.
Anti-tumour activity was observed in patients with previously treated renal cancer (partial response 5.4% and 48.7% with stable disease). Stable disease lasting more than 12 weeks was seen in 32.4% of renal patients. In the colorectal patients, stable disease lasting more than 12 weeks was observed in 24.3% of patients. No difference in efficacy was observed between the two arms of the study.
The safety profile was similar to that seen in AplidinÒ at the Phase I stage. The concomitant administration of L-carnitine allowed the administration of the higher 7 mg/m2 dose of AplidinÒ but resulted in more severe incidence of side effects, as compared to the 5 mg/m2 dose. These data support the continuation of the clinical development of AplidinÒ at a dose of 5 mg/m2 in renal cancer.
Yondelis(Trabectedin) The results of a combination Phase I study of carboplatin and YONDELISÒ (trabectedin) conducted in the UK and Spain in a total of 44 heavily pretreated ovarian patients will be presented. The data show that the combination was well tolerated and that the most common side effects observed were neutropenia and thrombocytopenia. Preliminary data on this study were presented at the ESMO congress in 2004.
Anti-tumor activity in ovarian cancer after failing other therapies was observed. Three partial responses (PR, 20%) and stable disease in 3 patients (SD, 20%) lasting longer than 3 months were observed, indicating that further study of the combination at the recommended dose is warranted.
This study shows that the combination of YONDELISÒ and carboplatin is feasible and active at doses near the maximum for both agents. This combination expands the potential use of YONDELIS in a variety of tumor types in which platinum compounds are the main chemotherapy agents.
The results of a Phase II trial of YONDELISÒ administered as a 3-hour intravenous infusion in sarcoma patients also will be presented. A total of 75 patients with Soft Tissue Sarcomas (STS), Osteosarcomas (OS), Rhabdomyosarcomas (RMS) or the Ewing’s Family tumors (EFT) were enrolled and treated in several European countries, having progressed through standard therapy. Preliminary results were presented at ASCO in 2003.
The final results in STS demonstrated that YONDELISÒ as a 3-hour infusion is a well-tolerated and active agent in this STS population. The data suggests the anti-tumor effect falls within the same range as the 24-hour continuous infusion, a regimen known to be active in STS (pivotal study STS-201 currently under registration). In addition, the longest response was observed in a patient with a myxoid liposarcoma, which has recently been shown to be sensitive to this agent. In EFT and RMS, some anti-tumor activity was observed, meriting further investigation.
Commenting on the ESMO presentations, Dr Miguel A. Izquierdo, PharmaMar’s Director of Clinical Development, said:
“The Kahalalide F data confirm the excellent tolerability profile reported in previous studies and establish that this compound class warrants further clinical evaluation in combination to exploit its therapeutic index. The promising activity observed with AplidinÒ in renal cancer and the fact that it is an inhibitor of the VEGF pathway, which is known to be relevant in renal cancer, makes the development of the compound in renal cancer a priority, particularly in combination with established anti-angiogenic drugs in this type of cancer. Aplidin remains in full development in solid and haematologic tumors and in pediatric cancer.
“The latest data on Yondelis confirm its anti-tumor activity in various sarcomas. They also demonstrate its potential as a combination therapy with carboplatin and its possible use in a variety of tumours where carboplatin is part of the standard chemotherapy treatment.“