Dana-Farber Led Phase I/II Combo Study Shows Results in Ovarian Cancer

Ovarian Cancer Therapy

The recent results of a Phase I/II clinical trial reveal that a niraparib and pembrolizumab combination across several subgroups, was well tolerated and evidenced promising antitumor activity in patients with recurrent ovarian carcinoma.  The lead investigators now advocate for more trials.

Preclinical Background

A lead investigator reports that “preclinical models, including those for ovarian carcinoma, have demonstrated a synergistic antitumor effect with niraparib and anti-PD-1 drugs regardless of BRCA mutation status or PD-L1 expression” noted Panagiotis A. Konstantinopoulos, MD, PhD, of the Dana-Farber Cancer Institute in Boston.  Perhaps this synergy could involve several mechanisms, including the ability of PARP inhibitors to upregulated PD-L1 expression reports Dave Levitan of Cancer Network.

The Study

The Phase I portion involved nine patients, while a Phase II included 53 patients—all with recurrent ovarian carcinoma—regardless of BRCA mutation status. The final efficacy analysis includes 60 available patients.  At a median age of 60, most patients had an ECOG performance status of 0 (71%).  Cancer Network reports the median number of prior lines of therapy was 3—and 63% had received bevacizumab.  The study was published in JAMA Oncology.

The Results

  • Median follow-up 12.4 months
  • Confirmed objective response rate of the full cohort 18%
  • 8 partial responses
  • 28 patients had stable disease
  • Disease control rate of 65%
  • 20 patients had progressive disease
  • Median duration of response was not yet reached in the trial
  • 8 patients had a response lasting longer than 6 months
  • 4 patients achieved a response lasting longer than 9 months

The combination therapy showed activity despite BRCA mutation status or homologous recombination deficiency (HRD) status, with similar objective response rates for all biomarker-defined populations reported Levitan.

The authors noted during the study that “Response rates were similar regardless of platinum status or bevacizumab treatment.” The PFS was 3.4 months while 6-month PFS rate landed at 31% while at 12 month end the rate was 12%. Overall survival data is not yet ready.

Adverse Events

The most common reported events include: Fatigue (53%), nausea (42%) and anemia (36%). Treatment-related AEs of grade 3 or higher included anemia (21%) and thrombocytopenia (9%).  A total of 10 patients (19%) experienced immune-related AEs related to treatment, with only three patients experiencing such events at grade 3 or higher.

Niraparib (Zejula) Background

An orally active, small molecule PARP inhibitor developed by Tesaro (GSK) to treat ovarian cancer. It was granted fast track designation by the FDA and Tesaro submitted an NDA in 2016. It was approved  by March 2017 in the US and in Europe in November 2017


GSK, an industry sponsor, was involved with this clinical trial.


Authors concluded “the study has shown that the combination treatment of niraparib and an anti-PD-1 antibody appears to be well tolerated and potentially offers clinical activity by tumor shrinkage and disease stabilization in patients with recurrent ovarian carcinoma.”

Lead Research/Investigator

Panagiotis A. Konstantinopoulos, Dana-Farber, Boston, MA