Merck hasn’t had much luck pairing cancer superstar Keytruda with PARP inhibitor Lynparza. But after flunking three clinical trials with the combination, the company has emerged with a tepid win with the pairing in ovarian cancer.
The phase 3 KEYLYNK-001 study, which evaluates Keytruda plus chemotherapy, followed by Lynparza maintenance, with or without Avastin, has met its primary endpoint, staving off progression of the disease. The regimen was tested as a first-line treatment for patients with BRCA non-mutated advanced epithelial ovarian cancer.
But while the combo racked up a statistically significant and clinically meaningful improvement in progression-free survival (PFS) over chemotherapy alone, it did not reach its secondary endpoint of overall survival (OS), according to analysis conducted by an independent data monitoring committee.
The role of Keytruda in the “intention-to-treat population remains uncertain at this time,” Merck said in a release, adding that it will present the results at an upcoming medical conference and discuss them with regulatory authorities.
Lynparza has been approved either by itself or with Avastin as a first-line maintenance treatment for ovarian cancer with certain mutations. With KEYLYNK-001, Merck is trying to add Keytruda on top of chemo before maintenance Lynparza comes in and reach BRCA-nonmutated patients.
The trial has another arm utilizing Keytruda plus chemotherapy, followed by Keytruda and placebo. In its Monday release, Merck didn’t say how that arm performed.
“For people living with ovarian cancer, there remains an unmet need for new treatment options that have the potential to improve outcomes,” Gursel Aktan, Merck Research Laboratories’ VP for global clinical development, said in a statement. “KEYLYNK-001 is the first positive phase 3 trial for Keytruda plus Lynparza, highlighting our commitment to research that may help address the global impact of women’s cancers.”
While Merck and co-developer AstraZeneca have lassoed approvals for Lynparza as a maintenance therapy for three different forms of ovarian cancer, Keytruda has yet to be endorsed in the indication.
In the U.S., it is estimated there will be approximately 19,680 patients diagnosed with ovarian cancer and about 12,740 deaths from the disease in 2024. The primary aim of first-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission, Merck said.
In March of this year, Merck reported that Keytruda plus Lynparza came up short in KEYLYNK-006, which evaluated the combo’s effectiveness to treat patients with metastatic non-small cell lung cancer. The regimen didn’t improve the life expectancy of patients and failed to significantly delay disease progression or death.
That readout came on top of Keytruda and Lynparza’s flop in nonsquamous non-small cell lung cancer in the KEYLYNK-008 study. Before that, in the KEYLYNK-010 trial, the regimen failed to perform better than an anti-androgen therapy in patients with previously treated metastatic castration-resistant prostate cancer.