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 2 portion of completed Phase 1/2 study in prostate cancer:

This was a single-arm Simon Optimum design Phase 2 study of zoptarelin doxorubicin in 25 patients with CRPC. Patients received zoptarelin doxorubicin (210 mg/m2) intravenously over 2 hours, every 3 weeks. The primary endpoint was CB, defined as remaining progression-free by RECIST and PSA after treatment for 12+ weeks. Secondary endpoints were progression free survival (PFS), best overall response, toxicity, pain and overall survival (OS).


Twenty patients had measurable disease, with a median of 1 prior chemotherapy regimens and a median PSA of 255.8 ng/ml. Eleven patients experienced CB; 13 patients achieved stable disease. Median PFS and OS were 4.4 months (95% CI: 3.6, 5.5) and 6 months (95% CI: 4.2, 10.7) respectively. Forty-four percent of patients demonstrated improvement of pain score at 12 weeks. Maximal PSA response was stable in 20 patients. Zoptarelin doxorubicin demonstrated good tolerability with grade 3‑4 hematologic (n=7) and grade 3 blood and lymphatic system disorders (n=5) adverse events as the most common events.

Results were presented by lead investigator Jacek Pinski, MD, PhD, of the USC Norris Comprehensive Cancer Center, during a poster session at the 18th ECCO – 40th ESMO European Cancer Congress in Vienna, Austria, on September 28, 2015.

Titled, “A Phase 2 Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer”, Liu SV, Tsao‑Wei DD, Xiong S, Groshen S, Dorff TB, Quinn DI, Tai YC, Engel J, Hawes D, Schally AV, Pinski J, the poster is available at this link.

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.