Lynparza Demonstrates 72.2% Objective Response Rate in Phase III SOLO-3 Trial for Advanced Ovarian Cancer with gBRCA Mutations

AstraZenecaWith Merck & Co., Inc. at the 2019 American Clinical Conference recently held in ChicagoTumorDetailed data from the SOLO-3 Phase III clinical study of the targeted anticancer drug Lynparza (Lynparza, generic name: olaparib, olaparib tablets) for ovarian cancer were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting.

The results showed that Lynparza demonstrated robust efficacy compared with physician’s choice of chemotherapy in patients with germline BRCA1/2 mutation (gBRCAm)-positive advanced ovarian cancer who had previously received ≥2 prior chemotherapy regimens. The study was conducted with the United StatesFDAIt was agreed to conduct the study as a post-marketing commitment. Based on the study data, Lynparza is the first and only PARP inhibitor that demonstrates significantly superior efficacy compared to chemotherapy in this setting.

SOLO-3 is a randomized, open-label, controlled, multicenter Phase III study that enrolled a total of 266 patients with recurrent ovarian cancer harboring deleterious or suspected deleterious BRCA1 or BRCA2 mutations, who had previously received two or more prior chemotherapy regimens. In the study, patients were randomized in a 2:1 ratio to receive either Lynparza (300 mg tablets, twice daily) or physician’s choice of single-agent chemotherapy (paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine).

The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR), i.e.,TumorProportion of patients with tumor burden reduced to a prespecified percentage; key secondary endpoints include progression-free survival (PFS), time to second disease progression (PFS2), and overall survival (OS).

The results showed that the study met its primary endpoint, with the Lynparza treatment group demonstrating statistically and clinically significant improvement in ORR compared to the chemotherapy group (72.2% vs 51.4% [95% CI: 1.40–4.58], p=0.002). Furthermore, the study also met the key secondary endpoint of PFS, with the Lynparza treatment group showing statistically and clinically significant improvement in PFS compared to the chemotherapy group (median PFS: 13.4 months vs 9.2 months [HR=0.62], p=0.013).

In this study, the safety and tolerability profile of Lynparza was consistent with that observed in previous studies. The most common adverse events (incidence ≥20%) included nausea (65%) and fatigue/asthenia (52%),Anemia(51%), vomiting (38%), diarrhea (28%), neutropenia (23%), and abdominal pain (21%). The most common grade ≥3 adverse events included anemia (21%), neutropenia (10%), fatigue/asthenia (5%), and thrombocytopenia (4%). In the Lynparza treatment group, 48% of patients experienced dose interruptions due to adverse events (AEs), and 7% discontinued treatment, compared with 42% and 20%, respectively, in the chemotherapy group.

AstraZenecaTumorJos Baselga, Executive Vice President of Research and Development, stated, “This study demonstrates that Lynparza has the potential to provide a much-needed alternative treatment for patients with specific recurrent BRCA-mutated advanced ovarian cancer, offering efficacy superior to standard-of-care chemotherapy. This marks the fourth positive Phase II/III trial of Lynparza across multiple lines of therapy for advanced ovarian cancer. We look forward to working closely with regulatory authorities to incorporate these results into the prescribing information for Lynparza.”

Roy Baynes, Global Head of Clinical Development and Senior Vice President at Merck Sharp & Dohme (MSD), and Chief Medical Officer of MSD Research Laboratories, stated, “Lynparza is the first and only PARP inhibitor proven to be more effective than chemotherapy in patients with recurrent BRCA-mutated advanced ovarian cancer who have previously received two or more lines of chemotherapy. The positive results from the SOLO-3 study reaffirm AstraZeneca and MSD’s ongoing commitment to exploring potential treatment options that go beyond the current standard of care for BRCA-mutated advanced disease.”

Lynparza is a first-in-class, oral PARP inhibitor and the first targeted therapy to leverage defects in the DNA damage response (DDR) pathway, such as BRCA mutations, to selectively kill cancer cells, offering treatment for a broad range of tumors with DNA repair deficiencies.Tumorpotential.

Lynparza was approved in December 2014FDAApproved as the first PARP inhibitor to be marketed globally. To date, the drug has been approved in more than 60 countries worldwide, with indications including: maintenance treatment for platinum-sensitive recurrent ovarian cancer (regardless of BRCA status); first-line maintenance treatment for patients with BRCA-mutated advanced ovarian cancer who have achieved a response to platinum-based chemotherapy; and treatment for previously chemotherapied germline BRCA-mutated, HER2-negative metastaticBreast Cancer, locally advanced breast cancer.

AstraZeneca and MSD entered into a global strategic oncology collaboration in July 2017 to jointly develop and commercialize Lynparza and another MEK inhibitor, selumetinib, for the treatment of various types of tumors. Currently, the two parties are conducting an extensive clinical development program to investigate the use of Lynparza across a broad range ofTumorpotential, including breast cancer, prostate cancer, pancreatic cancer, etc.

In China, Lynparza was approved last August for maintenance treatment of platinum-sensitive recurrent ovarian cancer. This approval makes Lynparza the first targeted therapy approved for ovarian cancer in the Chinese market, marking the entry of China’s ovarian cancer treatment into the era of PARP inhibitors.BioValleyBioon.com）