Investigational Drug Showing Promise for Taxane-Resistant Ovarian Cancer

Investigational Drug Showing Promise for Taxane-Resistant Ovarian Cancer

August 26, 2015

A recent study shows that the investigational drug EP-100--a synthetic cytolytic peptide conjugated to a luteinizing hormone releasing hormone (LHRH) -- may be a treatment option for taxane-resistant ovarian cancer.

Ovarian cancer is known to be difficult to treat because it is often without symptoms until it reaches later stages. In addition to that challenge, some patients even experience resistance after being treated with taxane drugs such as paclitaxel. The good news is that a recent study shows that the investigational drug EP-100--a synthetic cytolytic peptide conjugated to a luteinizing hormone releasing hormone (LHRH) -- may be a treatment option for taxane-resistant ovarian cancer. EP-100 targets cells that overexpress LHRH receptors and kills by membrane disruption.

Results were first presented at the 2015 ASCO Annual Meeting on May 30, 2015 by Alpa M. Nick, MD, MS, Assistant Professor, and Principal Investigator, Robert Coleman, MD, Professor from the Department of Gynecologic Oncology and Reproductive Medicine at University of Texas MD Anderson Cancer Center.1 Working with researchers from Pennington Biomedical Research Center and Louisiana State University, they conducted this phase II trial to demonstrate synergy between EP-100 and paclitaxel. This randomized trial explored the efficacy, safety, and toxicity of EP-100 and paclitaxel in patients with advanced ovarian cancer.  

The methods included a "run-in” dose-escalation specified for six patients who were treated with EP-100 per dose level. The other 44 patients were randomly selected to receive weekly paclitaxel (80 mg/m2 IV) and biweekly EP-100 (30 mg/m2 IV, EP-100 + paclitaxel) versus weekly paclitaxel (80 mg/m2 IV). Unlimited prior regimens were allowed.

The primary endpoint was overall response rate (ORR) per a prior study called RECIST 1.1. The secondary endpoint was disease control rate (DCR = complete response [CR] + partial response [PR] + stable disease [SD]). For an improvement in ORR and DCR of at least 30% with EP-100 plus paclitaxel versus paclitaxel alone, a sample size of 20 patients per arm estimated confidence intervals (CIs) of 6%-47% (paclitaxel alone) versus 27%-73% (EP-100 + paclitaxel). Patients progressing on paclitaxcel were allowed to receive EP-100 (30 mg/m2 IV) plus continuation of paclitaxel (80 mg/m2 IV). The research team then assessed time to progression.

Of the 44 patients who were enrolled in the study, the ORR was 34.8% (EP-100 + paclitaxel: 95% CI: 16%-57.3%) versus 33.3% (P: 95%, CI 14.6%-57%). The DCR was 73.9% (EP-100 + paclitaxel: 95% CI 51.6%-89.8%) versus 71.4% (P: 95%, CI 47.8%-88.7%). All 44 patients were assessable for safety; 43.5% (EP-100 + paclitaxel) and 47.6% (paclitaxel) had grade 3 or 4 events, primarily gastrointestinal and related to underlying disease.

The researchers concluded that EP-100 sensitizes paclitaxel-resistant ovarian tumors, leading to further shrinkage of target and nontarget lesions, which warrants a larger study comprising paclitaxel-resistant patients.

Esperance Pharmaceuticals, Inc. recently announced that it has entered into an agreement with MD Anderson Cancer Center to accelerate the clinical development of its lead anticancer candidate EP-100 for the treatment of ovarian cancer. They will also collaborate on preclinical studies with EP-100 as a treatment for breast cancer.2

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