MSD gets first positive trial of Keytruda/Lynparza combo

MSD's efforts to combine cancer immunotherapy Keytruda with its AstraZeneca-partnered PARP drug Lynparza have so far failed – but at last it can point to a partial win in a phase 3 trial.

The new data comes from the KEYLYNK-001 study evaluating Keytruda (pembrolizumab) and chemotherapy followed by Lynparza (olaparib) maintenance therapy with or without bevacizumab in patients with advanced epithelial ovarian cancer without BRCA mutations.

Compared to chemotherapy alone, Keytruda and Lynparza extended the time to disease progression or death, which MSD – known as Merck & Co in the US and Canada – said was "statistically significant and clinically meaningful."

It isn't a home run for the combination, however, as it wasn't able to improve overall survival, considered to be a more robust clinical endpoint, while MSD has acknowledged that "the role of Keytruda in the intention-to-treat population remains uncertain at this time."

Lynparza has been FDA-approved since 2018 for use with or without bevacizumab – sold by Roche as Avastin – as a maintenance therapy for epithelial ovarian cancer BRCA mutations who have responded to first-line chemotherapy based on the results of the SOLO-1 trial.

KEYLYNK-001 is attempting to extend the use of the PARP inhibitor into the non-BRCA population through the addition of PD-1 inhibitor Keytruda to the first-line regimen.

"For people living with ovarian cancer, there remains an unmet need for new treatment options that have the potential to improve outcomes," commented Gursel Aktan, Merck Research Laboratories' head of global clinical development.

"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," she added. MSD has said it will discuss the findings with regulatory authorities.

The result follows disappointing results for other trials of Keytruda with Lynparza, including KEYLYNK-010 in previously treated metastatic castration-resistant prostate cancer (mCRPC), as well as KEYLYNK-006 and KEYLYNK-008, respectively in non-squamous and squamous non-small cell lung cancer (NSCLC).

The negative results have not had much of an effect on Keytruda, which has dozens of indications that have driven sales to more than $25 billion a year, but will be disappointing for MSD and AZ's aspirations for Lynparza, which is currently seeing a slowdown in growth. Lynparza's worldwide sales rose 10% to $2.2 billion in the first nine months of the year.

AZ is also testing the PARP inhibitor in combination with its PD-L1 inhibitor Imfinzi (durvalumab) and claimed its first regulatory approval for the duo in the summer with a green light from the European Commission in previously untreated mismatch repair proficient endometrial cancer.

Photo by National Cancer Institute on Unsplash