AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) announced positive results from the randomised, open-label, controlled, Phase III SOLO-3 trial of Lynparza (olaparib) tablets in 266 patients with relapsed ovarian cancer after two or more lines of treatment. The trial was conducted as a post-approval commitment in agreement with the US Food and Drug Administration (FDA). This is the fourth Phase III trial to demonstrate a positive result for Lynparza. AstraZeneca and MSD now plan to discuss these results with the FDA.
Results from the trial showed BRCA-mutated (BRCAm) advanced ovarian cancer patients treated with Lynparza following two or more prior lines of chemotherapy demonstrated a statistically-significant and clinically-meaningful improvement in the primary endpoint of objective response rate (ORR) and the key secondary endpoint of progression-free survival (PFS) compared to chemotherapy. The safety and tolerability profile of Lynparza was consistent with previous trials.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: “We are very excited about SOLO-3, which is the first Phase III trial for a PARP inhibitor to demonstrate a positive result versus chemotherapy in advanced ovarian cancer where effective options are needed. We look forward to sharing the full results at a forthcoming medical meeting.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “Following on the US approval of Lynparza as first-line maintenance therapy for certain patients with BRCAm advanced ovarian cancer, the results of SOLO-3 further reinforce the efficacy of Lynparza in relapsed patients with gBRCAm advanced ovarian cancer following multiple lines of chemotherapy.”
SOLO-3 is a Phase III randomised, open-label, controlled, multicentre trial to evaluate the efficacy and safety of Lynparza tablets following two or more prior lines of chemotherapy. The trial randomised 266 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation. Eligible patients were randomised (2:1) to receive Lynparza 300mg tablets twice daily or physician’s choice single-agent chemotherapy (paclitaxel, topotecan, pegylated liposomal doxorubicin or gemcitabine). The primary endpoint was ORR by blinded independent central review and key secondary endpoints included progression-free survival, time to second disease progression or death and overall survival.
Lynparza is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of tumour types with defects and dependencies in the DDR.
Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.
About ovarian cancer
Ovarian cancer is a leading cause of cancer death in women worldwide, with a five-year survival rate of 19%. In 2018, there were over 295,000 new cases diagnosed and around 185,000 deaths. For newly-diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.[3-6]
About BRCA mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.