A Phase 2 clinical trial will assess for the first time whether the combination of the immunotherapy drug Keytruda (pembrolizumab) with two other drugs that have already been approved for ovarian cancer — Avastin (bevacizumab) and Cytoxan (cyclophosphamide) — can benefit patients with ovarian, fallopian tube, or peritoneal cancer.
The study is also the first analyze patients’ microbiomes to identify possible correlations between bacteria composition and tumor responses.
Keytruda has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma, non-small cell lung cancers, and recurrent head and neck squamous cell carcinoma. In ovarian cancer, however, the small number of patients who received the drug as a single therapy showed only modest responses.
But the study’s principal investigator, Emese Zsiros, MD, PhD, believes there is a strong rationale supporting the addition of Keytruda to the two ovarian cancer drugs, and that this combination may show a much broader effect than Keytruda therapy alone.
“Our biggest hope is that by trying these three drugs in combination, we can significantly extend the lives of patients with recurrent ovarian cancer. We also hope to minimize the side effects associated with chemotherapy drugs, and to markedly improve the quality of our patients’ lives,” Zsiros, assistant professor of oncology at Buffalo, New York’s Roswell Park Cancer Institute’s Department of Gynecologic Oncology and Center for Immunotherapy, said in a press release.
“We will be looking at potential biomarkers that will tell us who can most benefit from this therapy combination and to better understand how cancer cells and immune cells communicate with one another so that we can design better medications to kill cancer efficiently,” Zsiros said.
The open label, single arm Phase 2 study (NCT02853318), which is currently recruiting participants, is expected to enroll 40 patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Patients will receive Keytruda plus Avastin on day 1 and low-dose Cytoxan on days 1-21, in three-week cycles for up to 17 cycles or until disease progression or unacceptable toxicity.
The study’s primary endpoint is progression-free survival and incidence of adverse events, and secondary endpoints include overall survival, anti-tumor response, and objective tumor response, according to the modified RECIST 1.1 criteria.
In addition, researchers will also examine the blood, stool, vaginal, and skin microbiome samples to assess if changes in bacterial composition may be associated with responses to treatment or patient outcomes. This will be one of the first studies analyzing bacterial composition to look for possible associations with the response to immunotherapy agents in cancer patients.
“We’re looking at how to improve our immune defenses to cancer, but we’re looking at it from a variety of angles,” Zsiros said. “There’s a whole new area of research suggesting that what’s going on in our gut, our gut flora, has a huge influence on your overall health and happiness, and this study will extend that work into some new directions.”