Dana Farber Webchat: The Latest in Ovarian Cancer Treatment & Research

The latest developments in ovarian cancer treatment and research are addressed in the video below via a Dana-Farber Cancer Institute webchat that was conducted on September 16, 2014.

The Susan F. Smith Center for Women’s Cancers at the Dana-Farber Cancer Institute conducted a live video webchat panel with Ursula Matulonis, M.D., medical director of the Gynecologic Oncology Program, and gynecologic oncologists Panos Konstantinopoulos, M.D., Ph.D., and Susana Campos, M.D., MPH. The live webchat was held on September 16, 2014.

The general webchat topics addressed by the Dana-Farber doctors are listed below. For your convenience, we also provided the approximate video start time associated with each discussion topic. The entire video runs 49 minutes and 20 seconds.

  • Various types/subtypes of ovarian cancer and treatment differences. [1:40 minutes]
  • CA-125 and other ovarian cancer biomarkers. [5:10 minutes]
  • Areas of ongoing ovarian cancer research. [9:28 minutes]
  • Ovarian cancer treatment alternatives to standard of care chemotherapy. [13:55 minutes]
  • PARP Inhibitors & Immunotherapy. [15:03 minutes]
  • Mechanisms to reverse platinum drug resistance. [17:15 minutes]
  • Correlation between ovarian cancer and HPV (Human papillomavirus). [19:30 minutes]
  • The use of clinical trials for the treatment of ovarian cancer. [19:43 minutes]
  • Stage 1 ovarian cancer prognosis. [21:47 minutes]
  • Gene mutations related to hereditary ovarian cancer risk. [22:55 minutes]
  • Treatment options for platinum drug refractory/resistant ovarian cancer. [25:27 minutes]
  • Treatment of BRCA gene-mutated ovarian cancer patients. [27:50 minutes]
  • Ovarian cancer prevention. [30:18 minutes]
  • Promising treatments for ovarian clear cell cancer. [31:43 minutes]
  • Proper nutrition during and after ovarian cancer treatment. [33:47 minutes]
  • Symptoms associated with an ovarian cancer recurrence. [35:06 minutes]
  • Ovarian neuroendocrine cancer. [36:16 minutes]
  • Small-cell ovarian cancer. [39:22 minutes]
  • Origin of ovarian cancer. [42:41 minutes]
  • Treatment options for isolated or limited recurrent ovarian cancer tumors/lesions. [45:26 minutes]
  • Closing: Most Exciting Ovarian Cancer Developments. [47:07 minutes]


2011 ASCO: EC145 Demonstrates 85 Percent Improvement in Progression-Free Survival for Treatment of Platinum Resistant Ovarian Cancer

EC145, in combination with pegylated liposomal doxorubicin (Doxil®/Caelyx®) in patients with platinum-resistant ovarian cancer, met its primary endpoint by showing an 85 percent (2.3 month) improvement in median progression-free survival in the intent-to-treat population, and a 260 percent (4.0 month) improvement in a subset of folate receptor positive patients. The final EC145 phase 2 clinical study data were presented today at the 2011 American Society of Clinical Oncology Annual Meeting.

EC145 delivers a very potent vinca chemotherapy directly to cancer cells by targeting the folate receptor expressed on cancer cells, but not on most normal cells. Approximately 80-90 percent of ovarian and lung cancers express the receptor, as do many other types of cancer. Click on the picture above to view a video regarding EC145's mechanism of action. (Photo: Endocyte, Inc.)

Endocyte, Inc., a biopharmaceutical company developing targeted small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized therapy, today announced that the phase 2 PRECEDENT trial, which is investigating the company’s lead drug candidate, EC145, in combination with pegylated liposomal doxorubicin (PLD)(brand name: Doxil®/Caelyx®) in patients with platinum-resistant ovarian cancer, met its primary endpoint by showing: (i) an 85 percent (2.3 month) improvement in median progression-free survival (PFS) in the intent-to-treat population, and (ii) a 260 percent (4.0 month) improvement in a subset of folate receptor positive patients. EC145 in combination with PLD showed limited additional toxicity compared to standard therapy with PLD alone. The most commonly occurring adverse events were neutropenia, small intestine obstruction, and palmar-plantar erythrodysesthesia (or hand-foot syndrome). EC145 is a therapeutic that targets the folate receptor and EC20 is a companion imaging diagnostic used to assess folate receptor presence.

These final PFS data from the PRECEDENT trial were presented today at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), in Chicago, Illinois and are available at http://investor.endocyte.com/events.cfm.

“I am encouraged by these data as EC145 is the first drug candidate to demonstrate a significant improvement in PFS in a randomized trial of patients with platinum-resistant ovarian cancer, a very challenging disease with a high unmet need. Historical data show that for these patients on standard therapy, PFS is approximately three months and overall survival is approximately twelve months. No new drug has been approved in the U.S. for this indication in over a decade,” said Wendel Naumann, M.D., Associate Director of Gynecologic Oncology at Blumenthal Cancer Center, Carolinas Medical Center. “In addition the companion imaging diagnostic, EC20, is designed to identify patients who over-express the targeted receptor and are most likely to respond to EC145. This represents a personalized therapeutic approach that I believe will help oncologists direct patients to the most promising treatment.”

EC145 Phase 2 PRECEDENT Clinical Study Data 

The Phase 2 PRECEDENT trial was an international, multi-center, randomized study of 149 women with platinum-resistant ovarian cancer. Patients were randomized to receive EC145 plus PLD or PLD alone at a standard dose until disease progression or death. The primary endpoint of the study was progression-free survival. Secondary endpoints included response rate and overall survival.

The EC145 phase 2 PRECEDENT trial results are summarized below.

  • 85 Percent (2.3 Month) Improvement in Median Progression-Free Survival for All Patients

Patients receiving EC145 in combination with PLD, regardless of folate receptor expression, had a median progression free survival of 5.0 months compared to 2.7 months for patients receiving single agent PLD. The hazard ratio for PFS was 0.626 (p=0.031). The overall response rate was 28 percent in the EC145 combination group versus 16 percent in the PLD-alone group. CA-125 (cancer antigen-125) responses were also more common in patients receiving EC145 in combination with PLD compared to those receiving PLD alone, with response rates (based on CA-125 blood serum measurement) of 38 percent and 19 percent, respectively.

  • 260 Percent (4.0 Month) Improvement in Median Progression-Free Survival for Patients Most Positive for Folate Receptor

The study also utilized EC20, an investigational companion imaging diagnostic that is designed to identify patients with folate receptor positive tumors. As expected, in the folate receptor positive patients the improvement in PFS was even greater. In the subpopulation most positive for the folate receptor, PFS increased 4.0 months from 1.5 months to 5.5 months. The hazard ratio for PFS was 0.381 (p=0.018). This represents more than a 60 percent reduction in the risk of progression and provides evidence supporting the mechanism of action through targeting of the folate receptor. The overall response rate was 22 percent in the EC145 combination group versus 7 percent in the PLD alone group. CA-125 responses were also more common in patients receiving EC145 in combination with PLD compared to those receiving PLD alone, 43 percent and 13 percent, respectively.

“We see tremendous potential for continued development of EC145 based on these data that demonstrate, for the first time, a significant improvement in PFS in patients with platinum resistant ovarian cancer,” said Ron Ellis, President and Chief Executive Officer of Endocyte. “We have already advanced EC145 into Phase 3 evaluation with the PROCEED trial, which has a similar design to the PRECEDENT trial, and plan to file for regulatory approval in the European Union based on the PFS data from the PRECEDENT study.”

Plan to File PRECEDENT Data for Conditional Approval in Europe

As a result of Endocyte’s interaction with the European Medicines Agency (EMA), including a meeting with the Scientific Advice Working Party and written advice from the Committee for Medicinal Products for Human Use (CHMP), the Company will prepare marketing applications for both EC145 and EC20. Based on feedback from the CHMP, Endocyte plans to seek conditional marketing authorization for patients with platinum-resistant ovarian cancer who test positive for the folate receptor using the EC20 companion imaging diagnostic.

Phase 3 PROCEED Trial Initiated

Endocyte recently announced the initiation of patient enrollment in the Phase 3 PROCEED trial of EC145, which is structured to replicate the PRECEDENT trial design. The Phase 3 trial is a randomized, double-blinded trial of EC145 in combination with PLD compared to PLD plus placebo. The patient population — those with platinum-resistant ovarian cancer — will be the same as in the PRECEDENT trial, and the primary endpoint will be progression-free survival in patients selected by EC20 as folate-receptor positive. The trial will also be statistically powered for overall survival as a secondary endpoint with projected enrollment in excess of 500 patients. The trial will be conducted in approximately 150 sites in the U.S., Canada, and Europe.  More information regarding the trial is available at www.clinicaltrials.gov.

About EC145

EC145 is a conjugate of the vitamin folate and a super-potent vinca alkaloid. Folate is required for cell division and rapidly dividing cancer cells often over-express folate receptors in order to capture enough folate to support cell division. By attaching a chemotherapy drug to folate through proprietary chemistry, EC145 targets cancer cells while avoiding most normal cells. This targeted approach is designed to provide treatment with super-potent drugs while lowering toxicity compared to standard chemotherapy.

About EC20

EC20 is a folate-targeted molecular imaging agent that is being developed as a non-invasive method to identify tumors that over-express folate receptors. These tumors are the molecular target of Endocyte’s folate-targeted therapeutic compounds such as EC145. To date, EC20 has been administered to over 500 patients and has been found to be well tolerated.

About Endocyte

Endocyte is a biopharmaceutical company developing targeted therapies for the treatment of cancer and inflammatory diseases. Endocyte uses its proprietary technology to create novel small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized targeted therapies. The company’s SMDCs actively target receptors that are over-expressed on diseased cells, relative to healthy cells. This targeted approach is designed to enable the treatment of patients with highly active drugs at greater doses, delivered more frequently, and over longer periods of time than would be possible with the untargeted drug alone. The companion imaging diagnostics are designed to identify patients whose disease over-expresses the target of the therapy and who are therefore more likely to benefit from treatment.


  • EC145 PRECEDENT Trial Results — 2011 American Society of Clinical Oncology Annual Meeting Poster Presentation, June 5, 2011. [Adobe Reader PDF document]
EC145 PROCEED Clinical Trial Information:
Related Libby’s H*O*P*E* Video:
Related Libby’s H*O*P*E*™ Postings:

Experimental Drug NVP-BEZ235 Slows Ovarian Cancer Growth in Mice; Solid Tumor Clinical Trials Ongoing

A study conducted recently at UCLA’s Jonsson Comprehensive Cancer Center found that experimental drug NVP-BEZ235, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

A study conducted recently at  UCLA’s Jonsson Comprehensive Cancer Center (JCCC) found that an experimental drug, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

Oliver Dorigo, M.D., Ph.D., Assistant Professor, Department of Gynecologic Oncology, Division Gynecologic Oncology, UCLA Jonnson Comprehensive Cancer Center; Member, JCCC Cancer Molecular Imaging Program Area

The Novartis Oncology drug, called NVP-BEZ235, also inhibits growth of ovarian cancer cells that have become resistant to the conventional treatment with platinum chemotherapy and helps to resensitize the cancer cells to the therapy. In addition, it enhances the effect of platinum chemotherapy on ovarian cancer cells that are still responding to the therapy, said the study’s senior author, Dr. Oliver Dorigo, an assistant professor of obstetrics and gynecology and a JCCC researcher.

“Platinum-based chemotherapy drugs are effective in treating ovarian cancers as long as the cancer cells remain sensitive to platinum,” Dorigo said. “But once the tumor becomes resistant, treating the cancer becomes very challenging. This is a significant clinical problem, since the majority of ovarian cancer patients develop resistance at some point during treatment. Breaking chemotherapy resistance is a difficult challenge, but crucial if we want to improve long-term survival for our patients.”

The study, performed on cells lines and mouse models, appears in the April 15 issue of the journal Clinical Cancer Research.

Over the last several years, Dorigo has been working in his laboratory to develop new therapies for ovarian cancer. About 22,000 American women are diagnosed each year with ovarian cancer, and more than 14,000 deaths are attributed to the disease annually. Dorigo has focused his research efforts on a pathway called PI3Kinase/Akt/mTOR, which, once activated, promotes ovarian cancer growth. The activated pathway also makes the cancer more aggressive and more likely to spread to other organs, Dorigo said, so targeting it offers great promise for more effective therapies for the disease.

In this two-year study, Dorigo and postdoctoral fellow Chintda Santiskulvong found that inhibiting two checkpoints of the pathway — PI3Kinase and mTOR — with NVP-BEZ235 decreased cancer growth, both in cell culture dishes and in mice with ovarian cancer. It also significantly increased survival in the mice, he said. More importantly, NVP-BEZ235 slowed growth of the ovarian cancer cells that had become resistant to platinum and helped to break that resistance.

“We were very encouraged to find that NPV-BEZ235 could resensitize the ovarian cancer cells to standard platinum treatment,” Dorigo said. “In addition, we found this drug to be more effective in inhibiting ovarian cancer cell growth than other drugs that target only one checkpoint, mTOR, in this pathway. We believe that NVP-BEZ235 has superior efficacy because of the dual effect on PI3Kinase and mTOR.”

The experimental drug is being tested as a single agent at the Jonsson Cancer Center in human clinical trials against other solid tumors. Researchers involved with those studies have said early results are encouraging.

John Glaspy, M.D., M.P.H., Co-Chief, Department of Medicine, Hematology/Oncology, UCLA Jonnson Comprehensive Cancer Center; JCCC Director, JCCC Clinical Research Unit; Member, Stand Up To Cancer Mangement Committee

“This is clearly a promising agent with activity in humans,” said Dr. John Glaspy, a professor of hematology–oncology and a Jonsson Cancer Center scientist involved with the studies. “We are still assessing its tolerability in patients.”

Dorigo said he hopes to initiate a clinical trial for women with ovarian cancer that tests the combination of NVP-BEZ235 with platinum chemotherapy, as he believes that the combination might be more effective than each drug alone.

The study was funded by the Ovarian Cancer Research Foundation/Liz Tilberis Scholarship, the Gynecologic Cancer Foundation/Florence and Marshall Schwid Ovarian Cancer Award, a STOP Cancer Career Development Award and the National Institutes of Health’s Women’s Reproductive Health Research Program.

About the UCLA Jonnson Comprehensive Cancer Center

UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years.


Clinical Trial Information: