AEZS-108 is a targeted cytotoxic peptide conjugate which is a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by the LHRH receptor-positive tumors. The binding of conjugate molecule AEZS-108 to cancerous cells that express these receptors results in its accumulation in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug, doxorubicin, in the cells. Therefore, since they target specific cells, cytotoxic conjugates are postulated to be more effective and have less side-effects than the respective non-conjugated/non-linked cytotoxic agents in inhibiting tumor growth.

AEZS-108 is the first drug in a clinical study that targets the cytotoxic activity of doxorubicin specifically to LHRH-receptor expressing tumors.

Results - Phase 2 study in ovarian cancer: 

On June 6, 2010, positive efficacy and safety data for our doxorubicin targeted conjugate compound, AEZS-108, in ovarian cancer were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. 42 patients with platinum-resistant ovarian cancer entered the study. Patients received a recommended dose of 267 mg/m² by intravenous infusion over 2 hours, with retreatment every 3 weeks, for up to 6 courses. Response rate (RECIST and/or GCIG criteria) was defined as primary endpoint. Secondary endpoints were safety, time-to-progression (TTP) and overall survival (OS).

Results:

Efficacy included partial response in 5 patients (11.9%) and stable disease for more than 12 weeks in 11 patients (26.2%). Based on those data, a Clinical Benefit Rate (CBR) of 38% can be estimated. Median time to progression (TTP) and overall survival (OS) were 3.5 months (104 days) and 15.6 months (475 days), respectively.

Conclusions:

• AEZS-108 was active and well tolerated in patients with heavily pre-treated platinum and taxane resistant ovarian cancer;
• The safety profile confirmed the dose of 267 mg/m²;
• Hematological toxicity was rapidly reversible;
• Non-hematological toxicities were usually limited to lower severity;
• Tolerability and CBR compare favourably with topotecan and liposomal doxorubicin;
• Overall survival is encouraging as all patients treated with AEZS-108 were platinum-resistant.

Results - Phase 1 study in gynecological cancers:

On June 3, 2007 positive results of an open, multi-center, sequential group, dose-escalation Phase 1 study in various gynecological cancers were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 17 patients with LHRH receptor-positive ovarian, endometrial or breast cancers were recruited. AEZS-108 was administered by intravenous infusion over two hours at dosages of 10, 20, 40, 80,160 and 267 mg/m2. At 160 mg/m2, six patients had a total of 32 cycles and at 267 mg/m2, seven patients had a total of 27 cycles. Most of the patients had been pretreated with various chemotherapies.

The study showed that AEZS-108 was well tolerated by patients with gynecological tumors. Signs of anti-tumor activity were observed in seven out of 13 patients treated with 160 or 267 mg/m2 of AEZS-108, including three patients with complete or partial response.

Ongoing open-label, non-comparative multi-center Phase 2 trial will involve up to 82 women with LHRH receptor-positive ovarian and endometrial cancerous tumors. Its primary endpoint is the partial or complete tumor response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) and/or Gynecologic Cancer Intergroup Guidelines (GCIG). The trial is being conducted in 15 centers in Europe. Preliminary postive results for both indications have been disclosed and will be presented at upcoming conferences throughout 2010. AEZS-108 has been granted orphan-drug designation by the FDA for ovarian cancer.

Click here for further information about the AEZS-108 ovarian and endometrial cancers clinical study including a list of clinical sites.