USA – Merck & Co. has halted a Phase 3 trial testing a combination of two widely used cancer drugs, Keytruda and Lynparza, in patients with advanced prostate tumors due to disappointing study results.

The study, KEYLYNK-010 looked at Keytruda and Lynparza in patients whose cancer had progressed after treatment with chemotherapy and hormone therapy.

However, after reviewing interim data, a trial monitoring board determined that the regimen did not significantly prolong patients’ lives or slow tumor growth. The combination was also linked to more severe side effects rated 3 to 5.

After the interim analyses of the phase 3 KEYLYNK-010 trial revealed negative results, Merck decided to terminate the trial early in accordance with the recommendation of an independent data monitoring committee.

The failure is surprising given that Lynparza monotherapy has been approved for the treatment of patients with homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed after prior treatment with Xtandi or Zytiga.

It also follows a Lynparza victory in newly diagnosed mCRPC. The Poly (ADP-ribose) polymerase (PARP) inhibitor developed by AstraZeneca demonstrated that when combined with Zytiga and a steroid, it reduced the risk of disease progression or death by 34% in that patient group, regardless of gene mutation status.

Big setback to Merck

The study’s cancellation is a setback for Merck’s two-drug regimen. Merck paid AstraZeneca billions of dollars for partial rights to Lynparza in 2017.

Despite the prostate cancer miss, Merck has multiple KEYLYNK studies evaluating the Keytruda-Lynparza combination in different lung cancer settings, ovarian cancer, triple-negative breast cancer, and across solid tumors with specific biomarkers, according to the company.

In addition to its AstraZeneca collaboration, Merck is testing Keytruda in a variety of other mCRPC combinations.

Both Keytruda and Lynparza are regarded as market leaders in their respective fields—Keytruda is the undisputed programmed cell death protein-1 (PD-1) king, and Lynparza is the best-selling PARP inhibitor.

In the phase 3 Keynote-921 trial, the popular PD-1 inhibitor is combined with chemotherapy in patients who have progressed on next-generation hormonal agents such as Zytiga and Xtandi.

The trial is scheduled to conclude in September 2021, but Merck has yet to release the results.

Furthermore, Keynote-641 is determining whether Keytruda’s combination with Xtandi can defeat Xtandi alone in mCRPC.

Keytruda is being added to Xtandi and androgen deprivation therapy in another Keynote-991 study in patients with metastatic hormone-sensitive prostate cancer.

Meanwhile, Bristol Myers Squibb’s Opdivo, a PD-1 rival, has partnered with Clovis Oncology’s Rubraca, a PARP inhibitor that has underwhelmed due to commercial pressure from Lynparza and GlaxoSmithKline’s Zejula.

A phase 2 trial called CheckMate 9KD recently found that the Opdivo-Rubraca combination improved survival in patients with chemotherapy-naive mCRPC with homologous recombination deficiency.

AstraZeneca has also been combining Lynparza with its PD-L1 inhibitor Imfinzi. The phase 3 Duo-O study, which is testing Lynparza, Imfinzi, and Roche’s Avastin in ovarian cancer, is one area where it may clash with Merck.

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