The primary endpoint was a statistically significant improvement in progression-free survival for the combination versus platinum-based chemotherapy.
AstraZeneca and Merck announced that the Phase III GY004 trial of cediranib in combination with Lynparza compared to platinum-based chemotherapy in platinum-sensitive relapsed ovarian cancer failed to meet the primary endpoint.
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment focused against DNA damage response (DDR) pathway deficiencies, like those seen in BRCA mutations. Lynparza is being jointly developed and commercialized by AstraZeneca and Merck in a global strategic oncology collaboration announced in July 2018.
Cediranib is an investigational oral vascular endothelial growth factor receptor (VEGFR) inhibitor that blocks blood vessel growth that helps tumors to grow.
GY004 is an open-label, randomized, multicenter, Phase III trial evaluating cediranib and Lynparza or Lynparza alone compared to standard platinum-based chemotherapy in patients with recurrent platinum-sensitive ovarian cancer, fallopian tube, or primary peritoneal cancer patients. The trial included patients both with and without a BRCA mutation.
The trial is led by NRG Oncology, a non-profit research group funded by the National Cancer Institute (NCI) in collaboration with AstraZeneca. AstraZeneca provided both drugs through a Cooperative Research and Development Agreement with the NCI.
“Despite these disappointing results, we remain committed to expanding on the benefits already demonstrated with Lynparza for patients with advanced ovarian cancer,” said Jose Baselga, executive vice president, oncology R&D, AstraZeneca. “We will work closely with NRG Oncology and the NCI to review the full results to inform our ongoing research.”
The primary endpoint was a statistically significant improvement in progression-free survival (PFS) for the combination versus platinum-based chemotherapy. The NCI and NRG Oncology plan to present complete data at an upcoming medical conference.
“Ovarian cancer is one of the most difficult tumors to diagnose and treat early,” said Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “AstraZeneca, Merck and our partners will continue to explore ways to help patients through our joint clinical trial development program.”
Lynparza is indicated for a broad range of cancers, including first-line maintenance BRCA-mutated advanced ovarian cancer, maintenance recurrent ovarian cancer, advanced gBRCAm ovarian cancer, gBRCAm HER2-negative metastatic breast cancer, and first-line maintenance gBRCAm metastatic pancreatic cancer.
NRG Oncology is made up of more than 1,000 member sites, including institutions on five continents. It focuses on conducting multi-institutional clinical and translational research with an emphasis on gender-specific cancers including gynecologic, breast, and prostate cancers, as well as localized or locally advanced cancers of all types.
Three legacy groups, the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG) and the Gynecologic Oncology Group (GOG) formalized becoming NRG Oncology with a grant proposal to the National Cancer Institute. Together, the three groups have more than 150 years of cumulative experience running Phase II and III clinical trials sponsored mostly by the NCI. They also have a history of conducting Phase I trials and translational biological research.
The organization focuses on adult brain tumors, head and neck cancer, localized and locally advanced lung cancer, breast cancer, gastrointestinal cancer, including colorectal and noncolorectal, genitourinary cancer, with an emphasis on nonmetastatic prostate and bladder cancer, and gynecologic cancers, including ovarian, cervix, and endometrial.
