Phase 3 Trial Fails to Improve Progression-Free Survival in Previously Untreated Epithelial Ovarian Cancer

April 13, 2020

After failing to meet its primary endpoint of progression-free survival, the JAVELIN Ovarian PARP 100 clinical trial was stopped.

The phase 3 JAVELIN Ovarian PARP 100 clinical trial failed to meet its primary endpoint of improving progression-free survival in patients with ovarian cancer and has since been discontinued.

Researchers were examining the efficacy and safety of Bavencio (avelumab) in combination with chemotherapy followed by maintenance Bavencio in combination with Talzenna (talazoparib) in patients with locally advanced or metastatic ovarian cancer.

“The decision was based on several emerging factors since the trial’s initiation, including the previously announced interim results from JAVELIN Ovarian 100,” stated a press release from Merck KGaA and Pfizer, the companies that collaborated on the trial. “The alliance determined that the degree of benefit observed with avelumab in frontline ovarian cancer in that study does not support continuation of the JAVELIN Ovarian PARP 100 trial in an unselected patient population and emphasizes the need to better understand the role of immunotherapy in ovarian cancer.”

The phase 3 trial had an estimated enrollment of 720 patients who had either stage 3 or stage 4 epithelial ovarian, fallopian tube or primary peritoneal cancer and must have been eligible to receive Avastin (bevacizumab) in combination with platinum-based chemotherapy.

The primary endpoint of progression-free survival, which means a patient’s disease didn’t get worse during or after treatment or lead to death, was not reached.

The JAVELIN Ovarian 100 was exploring frontline Bavencio in 998 patients with locally advanced or metastatic (stage 3 or stage 4) epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who had never been treated before. Patients were randomly selected to receive carboplatin/paclitaxel, carboplatin/paclitaxel with maintenance Bavencio or Bavencio plus carboplatin/paclitaxel followed by maintenance Bavencio.

During an interim analysis, an independent data monitoring panel determined that neither of the two Bavencio groups would demonstrate a progression-free survival benefit over the control group of chemotherapy alone. In addition, there were no new safety signals.

Prior to the JAVELIN Ovarian 100 announcement, the companies also reported that results of the multicenter, phase 3 JAVELIN Ovarian 200 trial demonstrated that single-agent Bavencio or Bavencio plus pegylated liposomal doxorubicin (PLD) did not lead to a statistically significant improvement in overall survival or progression-free survival compared with PLD alone in patients with platinum-resistant/refractory ovarian cancer.

Bavencio is a type of immunotherapy that targets programmed death ligand-1 (PD-L1), a protein produced in excessive amounts by several cancers. By binding to PD-L1, the medication potentially triggers an immune response to attack the cancer cells.

Recently approved treatment options for patients with ovarian cancer, including the December 2018 approval of Lynparza (olaparib), a type of PARP inhibitor, also played a role in the companies’ decision to discontinue the trial.

“The alliance determined that the degree of benefit observed with avelumab in frontline ovarian cancer in that study does not support the continuation of the JAVELIN Ovarian PARP 100 trial in an unselected patient population and emphasizes the need to better understand the role of immunotherapy in ovarian cancer,” stated the press release. “Additional factors include the rapidly changing treatment landscape and the approval of a PARP inhibitor in the frontline maintenance setting.”


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