- Disappointing study results have led Merck & Co. to stop early a Phase 3 trial testing a combination of two widely used cancer drugs, Keytruda and Lynparza, in patients with advanced prostate tumors.
- The study, known as KEYLYNK-010, evaluated Keytruda and Lynparza in patients whose disease had progressed after treatment with chemotherapy and hormone therapy. However, after interim data checks, a trial monitoring board found the regimen didn't meaningfully extend patients' lives or slow tumor growth. The combination also was associated with more severe side effects.
- The study termination is a setback for a two-drug regimen Merck has prioritized. The combination's potential was a key reason Merck paid AstraZeneca billions of dollars for partial rights to Lynparza in 2017, and clinical trials are continuing in lung, ovarian and triple-negative breast cancers as well as other solid tumors.
Keytruda and Lynparza are each blockbuster cancer drugs. Merck's Keytruda, an immunotherapy approved for dozens of tumors, generated $17 billion in sales last year. AstraZeneca's Lynparza, also used to treat several cancers and the top-selling member of a group of medicines known as PARP inhibitors, earned almost $3 billion.
Both drugs work differently. Keytruda helps the immune system better recognize and attack cancer, while Lynparza targets a DNA repair enzyme that tumors co-opt.
Those potentially complementary mechanisms have led researchers to hypothesize the two could work well together. In 2017, Merck and AstraZeneca teamed up to co-develop Lynparza in an alliance worth as much as $8.5 billion. At the time, AstraZeneca CEO Pascal Soriot noted how the deal built on evidence that PARP blockers could be combined with immunotherapies. Both companies outlined plans to test their respective immunotherapies — for Merck, Keytruda and for AstraZeneca, Imfinzi — alongside Lynparza.
Since then, the partners have advanced their research across different tumor types. For example, AstraZeneca has late-stage studies underway testing Imfinzi and Lynparza-based regimens in ovarian and endometrial cancers as well as a Phase 2 trial in lung tumors. Merck has several Keytruda and Lynparza studies underway as well.
Separately, GlaxoSmithKline has run combination studies with its rival PARP blocker, Zejula.
However, Tuesday's announcement marks a setback as its the first result from the companies' Phase 3 programs. The study enrolled 793 patients, who were randomized and treated with either a combination of Lynparza and Keytruda or a hormone therapy they hadn't previously received.
Merck hoped to show the drug combination could keep patients alive and hold their tumors in check longer than another hormone drug. Instead, Keytruda and Lynparza missed both of the study's main goals.
While Merck didn't disclose details, the company said it plans to share specifics at an upcoming medical meeting.
As a monotherapy, Lynparza is approved for use in certain prostate cancer patients who haven't responded to at least one treatment. It's produced positive results in a Phase 3 study in newly diagnosed patients as well.