Merck's Keytruda dealt another blow in prostate cancer but readies new challenge to AZ's Imfinzi

In a split showing for cancer powerhouse Merck, its immunotherapy Keytruda continued a losing streak in prostate cancer but chalked up a win to pressure an industry-first approval by AstraZeneca.

Merck has called it quits on a phase 3 trial of Keytruda in metastatic hormone-sensitive prostate cancer after an independent data monitoring committee ruled that the study likely wouldn't be successful, the company said Wednesday.

The phase 3 KEYNOTE-991 trial tested Keytruda against placebo in their respective combinations with Astellas and Pfizer’s antiandrogen drug Xtandi and androgen deprivation therapy. At the interim analysis, the Keytruda regimen failed to improve patients’ life expectancy and didn’t show a benefit in slowing tumor progression.

KEYNOTE-991 marks the third phase 3 flop for Keytruda in prostate cancer in less than a year. In March 2022, Merck pulled the plug on the KEYLYNK-010 trial after interim results suggested the pairing of Keytruda and Lynparza didn’t work any better than an anti-androgen therapy in previously treated metastatic castration-resistant prostate cancer (mCRPC).

Then in August, a trial combining Keytruda with chemotherapy also failed to top chemo alone in mCRPC.

The three consecutive failures may serve as a warning sign for the blockbuster therapy.  But the New Jersey pharma remains headstrong about Keytruda’s potential in prostate cancer. Merck will “continue to advance our clinical development program to evaluate Keytruda-based combinations and novel candidates for patients with prostate cancer,” Scot Ebbinghaus, M.D., VP of clinical research at Merck Research Laboratories, said in a Wednesday statement.

Meanwhile, one of the three phase 3 prostate cancer trials that Merck talked up back in 2019 has yet to read out. The KEYNOTE-641 study evaluating Keytruda in combination with Xtandi in mCRPC bears a primary completion date this coming November.

While Keytruda suffered a defeat in prostate cancer, the popular PD-1 inhibitor registered a win to potentially challenge AstraZeneca’s Imfinzi in a rare cancer type.

The addition of Keytruda to standard chemotherapy showed a “statistically significant and clinically meaningful” improvement in patient survival versus chemo alone for patients with newly diagnosed biliary tract cancer, Merck said in a separate release Wednesday.

The success of the phase 3 KEYNOTE-966 trial puts Keytruda on track to compete with Imfinzi, which in September snagged the first FDA approval for any PD-1/L1 inhibitor in biliary tract cancer. In the phase 3 TOPAZ-1 trial, adding Imfinzi to chemo led to a 20% reduction in the risk of death.

If Keytruda shows better data than Imfinzi did in this cancer, the AZ drug likely wouldn't stand a chance in the commercial market because of Keytruda’s wide adoption across a broad range of tumor types.