Tesaro Inc., of Waltham, Mass., advanced its poly ADP-ribose polymerase (PARP) inhibitor, niraparib, for ovarian cancer into a Phase III. The double-blind, placebo-controlled trial, designated NOVA, began enrollment of patients with high-grade serous, platinum-sensitive, relapsed ovarian cancer.

A previous Phase I trial showed that at the recommended dose, three out of four patients achieved a RECIST response. The primary endpoint of the study will be progression-free survival (PFS).

Tesaro hasn't offered any guidance as to the length of the trial. President and co-founder Mary Lynne Hedley told BioWorld Today that the trial is multinational and "as such, we try to optimize the best trial sites with the fastest trial execution. It's always a balance of getting the right sites and the right patients and motivating them to enroll quickly."

The new trial is one of two Phase III trials covered by a recent partnership between Tesaro and Myriad Genetics Inc., of Salt Lake City. Under that agreement, Myriad agreed to carry out BRCA1 and BRCA2 mutation testing on patients in two Phase III studies of niraparib.

In addition to the current study in ovarian cancer, Myriad also will work with Tesaro on its planned Phase III study of niraparib in metastatic breast cancer patients who have germline BRCA mutations. That study is scheduled to begin in the second half of this year.

Tesaro has another partner for its ovarian cancer study, the European Network of Gynecological Oncological Trial Groups (ENGOT). ENGOT is working with Tesaro to optimize the protocol design and to accelerate and streamline selection of investigators and clinical site management in Europe, as well as expediting patient enrollment and data publication.

The NOVA trial will evaluate a single daily 300-mg dose of niraparib. Patients will be randomized 2-to-1 to receive niraparib or placebo and will be continuously treated until progression. In addition to the primary endpoint of PFS, the trial also will assess secondary endpoints including patient-reported outcomes, chemotherapy-free interval length and overall survival.

Tesaro's Phase I results are guiding its design for Phase III. In addition to the 75 percent response rate, which Hedley acknowledged represents "small numbers, but very compelling at this stage," the study also showed a RECIST response rate of 46 percent across all dose levels, and a RECIST response rate of 50 percent in patients with platinum-sensitive ovarian cancer and germline BRCA mutations.

Hedley said the trial participants are "enriched in a way for being sensitive to a PARP inhibitor" by virtue of being platinum-sensitive. Once that is established, testing for a germline BRCA mutation is a "second sort of enrichment process," she added. "We know based on other work with PARP inhibitors that patients that are germline BRCA are more susceptible to a PARP inhibitor."

The two groups, those with BRCA mutations and those without, are separated and enrolled in separate cohorts in the trial.

A number of companies are working on PARP inhibitors. Clovis Oncology Inc. recently unveiled results from an ongoing Phase I/II monotherapy study of rucaparib, a PARP inhibitor, that it is developing for ovarian cancer. First data from a Phase I dose-escalation study showed activity not only in ovarian tumors but also breast and pancreatic cancers.

Astrazeneca plc has also been active in the PARP area. It advanced its compound olaparib into Phase III, also using Myriad's BRCA test to stratify patients. Astrazeneca disclosed data showing that patients with BRCA-mutated ovarian cancers received the greatest clinical benefit from maintenance treatment with oalaparib.

Tesaro recently netted about $69.7 million in a public offering to advance its pipeline, which also includes rolapitant, for chemotherapy-induced nausea and vomiting, and TSR-011, for ALK-positive tumors, including non-small-cell lung cancer. (See BioWorld Today, Feb. 22, 2013.)