The 25% response rate seen in the trial — called TOPACIO (NCT02657889) — was superior to that seen in historical controls treated with either drug alone.
The study, “Phase 2 TOPACIO Data Demonstrate Activity in Platinum-Resistant and Platinum-Refractory Ovarian Cancer Patients, Regardless of Biomarker Status,” was presented at the 2018 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, held March 24-27 in New Orleans.
The trial was designed to test the safety and effectiveness of Zejula plus Keytruda in patients with recurrent, platinum-resistant ovarian cancer or triple negative breast cancer.
Typically, response to chemotherapy is 5-18% in patients with platinum-resistant ovarian cancer, and even lower in platinum-refractory patients.
Despite the introduction of new treatment approaches, including immune checkpoint inhibitors and PARP inhibitors, response rates in these patients remain low.
Indeed, patients with relapsed or refractory ovarian cancer show a 0-14% response rate to PARP inhibitors, such as Tesaro’s Zejula, depending on genetic biomarkers, and 10-15% to anti-PD-1 antibodies, such as Merck’s Keytruda.
“Patients with platinum-resistant or platinum-refractory ovarian cancer have limited treatment options available to them,” Mary Lynne Hedley, PhD, president and chief operating officer at Tesaro, said in a press release. “Approximately 10,000 women in [both] the US and EU begin treatment for platinum-resistant or refractory ovarian cancer each year.”
The TOPACIO trial was designed to test whether a combination of the two approaches could increase the proportion of patients responding to therapy. Zejula was given in oral tablets once daily, and Keytruda was given intravenously every three weeks.
From a total of 60 evaluable patients, 45% had received three or more prior lines of chemotherapy.
After treatment, 25% of patients had responded to the combination, and 68% had achieved at least stable disease. The response rates for platinum-refractory patients were also high, at 24%. And, response rates were not dependent on biomarker status.
The combination was also well-tolerated, with 9% of patients experiencing severe or life-threatening low platelet levels (thrombocytopenia). The other commonly observed adverse events were anemia (19%) and abnormally low blood levels of neutrophils (6%).
“Preliminary results from TOPACIO suggest the combination of [Zejula] and an anti-PD-1 antibody [Keytruda] could provide meaningful clinical benefit to these patients, regardless of biomarker status,” Hedley said.
“Planning of a registration study is underway to support approval of Zejula and TSR-042 combination therapy for these patients. TSR-042 is Tesaro’s anti-PD-1 antibody,” she said.
Marty Huber, MD, senior vice president and chief medical officer at Tesaro, said the trial data “provide a compelling initial step in our ovarian cancer development strategy which is progressing from monotherapy Zejula … to doublet and triplet combination approaches.
“Our ultimate goal is to maximize the benefit to women across the full spectrum of ovarian cancer,” Huber said.
Tesaro plans to present additional results from TOPACIO, including data from patients with platinum-resistant ovarian cancer and patients with triple-negative breast cancer, at the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting, coming up June 1-5 in Chicago.
Scientists also presented data from the Phase 3 ENGOT-OV16/NOVA study (NCT01847274), showing that body weight and platelet count at the start of treatment may predict life-threatening thrombocytopenia (a platelet deficiency in the blood) during Zejula treatment.
The retrospective study, “A Retrospective Analysis of Phase 3 ENGOT-OV16/NOVA Trial Identified Predictors of Early Dose Modification for Niraparib,” showed that patient body weight lower than 170 pounds (77 kilograms) or a platelet count of below 150,000/µL, are significant factors for grade 3/4 thrombocytopenia.
“This analysis provides physicians with new information to help quickly identify the most appropriate dose for each of their patients,” said Mansoor Raza Mirza, MD, the principal investigator of the ENGOT-OV16/NOVA trial. “This information is particularly important as we move towards combination treatment approaches with [Zejula], which are currently being studied in multiple ongoing clinical trials.”