Early-phase Trials Explore Novel Combinations for Ovarian Cancer

Building on recent discoveries at Dana-Farber/Brigham and Women’s Cancer Center using a variety of inhibitor combinations, researchers in the Susan F. Smith Center for Women’s Cancers are leading new early-phase trials for patients with ovarian cancer.

“We are looking at new targeted approaches for patients with ovarian cancer, using biomarkers and other key information to identify specific patient populations that are most likely to respond to certain treatments,” said Ursula Matulonis, MD, Director of the Center’s Gynecologic Oncology Program. “Given the genetic complexity of the most common type of ovarian cancer, serous cancer, our group thinks that combination therapies as a strategy are very promising.”

Findings in PARP Combination Studies

At the 2015 American Association for Cancer Research (AACR) Annual Meeting, Dr. Matulonis presented final results of a Phase I study of the combination of the poly ADP-ribose polymerase (PARP) inhibitor olaparib and the phosphatidylinositol- 3-kinase (PI3K) inhibitor BKM120 in patients with high-grade serous ovarian cancer, as well as triple-negative breast cancer. The study demonstrated the safety of the combination and showed efficacy in both BRCA-mutant and BRCA-wildtype cancers.

A previous multi-center Phase II trial, Combination Cediranib and Olaparib versus Olaparib Alone for Women with Recurrent Platinum-sensitive Ovarian Cancer (Lancet Oncol. 2014 Oct;15(11):1207-14), led by the overall Principal Investigator Joyce Liu, MD, MPH, and co-PI Dr. Matulonis compared the combination of olaparib and cediranib, an anti-angiogenic agent, with olaparib alone in patients with ovarian cancer. The trial not only showed that the combination was more active than olaparib alone but that activity was observed in both BRCA-mutation carriers and BRCA non-carrier participants.

New Early-phase Studies

The team is currently expanding its Phase I and Phase II trials using PARP inhibitors, immunotherapies, antibody drug conjugates, and other agents, to include new combinations and patient populations. Current and upcoming studies include:

  • Phase I/II trial of niraparib, a PARP inhibitor, plus pembrolizumab, an anti-PD-1 immunotherapy agent, in patients with ovarian and breast cancers. Site Principal Investigator: Panagiotis A. Konstantinopoulos, MD, PhD;
  • Phase I dose-expansion study of BYL719 or BKM120, both PI3K inhibitors, with olaparib in patients with high-grade serous ovarian cancer and recurrent triple negative breast cancer. National Principal Investigator: Ursula Matulonis, MD;
  • Phase I study of ricolinostat, an oral HDAC6 inhibitor, together with weekly paclitaxel in recurrent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer. Site Principal Investigator: Joyce Liu, MD, MPH;

(For information on these trials, please contact Christin Whalen, RN, at cwhalen@partners.org or (617) 582-7738)

“These early-phase studies enable us the ability to offer additional options for patients with advanced ovarian cancer and evaluate the effects of new drug types and combinations in extending survival,” said Dr. Liu.

  • Joyce Liu, MD, MPH
    Director of Clinical Research, Gynecologic Oncology Program, Susan F. Smith Center for Women’s Cancers, Dana-Farber/Brigham and Women’s Cancer Center
  • Ursula Matulonis, MD
    Director, Gynecologic Oncology Program, Susan F. Smith Center for Women’s Cancers, Dana-Farber/Brigham and Women’s Cancer Center

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