Zoptarelin Doxorubicin
Ovarian cancer (completed)

Castration and taxane-resistant prostate cancer

Therapeutic area


Target indication

Ovarian and prostate cancer

Development stage

Phase 2


Zoptarelin doxorubicin 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 zoptarelin doxorubicin 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.

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

Trial results

Results - Phase 2 study in ovarian cancer:

On June 6, 2010, positive efficacy and safety data for our doxorubicin targeted conjugate compound, zoptarelin doxorubicin, 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).


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.


  • Zoptarelin doxorubicin 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 zoptarelin doxorubicin were platinum-resistant.

Results - Phase 1 portion of ongoing Phase 1/2  study in prostate cancer:

On June3rd 2013, final encouraging results for the Phase 1 portion of the ongoing investigator-driven Phase 1/2 study in castration- and taxane-resistant prostate cancer (CRPC) were presented at the American Society of Clinical Oncology (ASCO) annual meeting. Data showed that zoptarelin doxorubicin was well tolerated and demonstrated promising antitumor activity in men with CRPC.

Patients received zoptarelin doxorubicin intravenously over 2 hours every 3 weeks for up to 6 cycles, until progression of the disease, unacceptable toxicity or patient withdrawal. Premedication included dexamethasone 8 mg.

18 men were treated at 3 dose levels: 160 mg/m2, 210 mg/m2, and 267 mg/m2. Overall, zoptarelin doxorubicin was well tolerated among this group of heavily pretreated patients. There were 2 dose limiting toxicities (grade 4 neutropenia and grade 3 febrile neutropenia) prompting de-escalation to 210 mg/m2 and establishing it as the Maximum Tolerated Dose. Among the 15 evaluable patients with measurable disease, 10 achieved stable disease and a drop in Prostatic Specific Antigen ("PSA") was noted in 3 patients.

The poster entitled, "A Phase I Dose-Escalation Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer", is available on ASCO's website at the following link.

For more information on the current Phase 2 portion of the trial which is supported by a three-year US$1.6 million grant from the National Institutes of Health to the lead investigator, Jacek Pinski, MD, PhD, of the USC Norris Comprehensive Cancer Center, is available at this link NCT01240629.

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. Zoptarelin doxorubicin 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 zoptarelin doxorubicin 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 zoptarelin doxorubicin, including three patients with complete or partial response.

Development plan

Zoptarelin doxorubicin has been granted orphan-drug designation by the FDA for ovarian cancer.

Zoptarelin doxorubicin is being studied in a Phase 2 investigator-driven trial in prostate cancer.

Furthermore, a Phase 3 trial in endometrial cancer is currently ongoing.

Partnership status

Aeterna Zentaris owns the worldwide rights.