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Merck plans trio of Phase 3 Keytruda studies in prostate cancer

  • Merck & Co. said Thursday it plans to launch three pivotal Phase 3 studies testing different combination therapies involving its blockbuster immunotherapy Keytruda in patients with a difficult-to-treat form of prostate cancer.
  • The big pharma’sdecision stemmed from Phase 1b/2 data out of an umbrella study of Keytruda in metastatic, castration-resistant prostate cancer (mCRPC), said Roy Baynes, chief medical officer at Merck Research Laboratories, in a statement. The results were presented at an oncology conference Thursday. 
  • The three pivotal Phase 3 studies will all assess overall survival as a co-primary endpoint, and the new studies give Merck the largest clinical program for an anti-PD-1 therapy in prostate cancer, the company claimed.

Checkpoint inhibitors like Merck’s Keytruda (pembrolizumab) have changed cancer care across a number of tumor types, but none are currently approved for prostate cancer. Neither are any of three PARP inhibitors currently on the U.S. market for ovarian and breast cancers. 

Merck hopes to change that through these late-stage studies, pairing Keytruda with the PARP inhibitor Lynparza (olaparib), chemotherapy and approved prostate cancer agent Xtandi (enzalutamide). 

Patients with mCRPC pose a particular challenge to treat. Metastatic cancer has spread to other parts of the body, while castration-resistant tumors have continued to grow despite surgery or treatment to lower the amount of male sex hormones, or androgens, that typically drive prostate cancer.

Current treatment options for this type of prostate cancer are led by Zytiga (abiraterone acetate), a Johnson & Johnson drug now facing generic competition, and Pfizer and Astellas’ Xtandi.

Merck’s Phase 1b/2 study tested four Keytruda combinations, pairing the immunotherapy with both of those current treatment options as well as with chemotherapy and with Lynparza, which is jointly owned by AstraZeneca and Merck.

Results presented Thursday came from a small number of patients, but showed some positive responses in previously treated patients.

In the Lynparza cohort, patients previously given chemotherapy and up to two anti-hormone therapies were enrolled. Data from 41 patients showed a prostatic specific antigen (PSA) response rate of 12% and an overall response rate of 7% — the study’s two primary efficacy endpoints. PSA response rate was defined as a confirmed decrease in PSA of 50% of greater. 

Patients in the Xtandi and chemothrapy cohorts had not previously received chemotherapy, but had been given some prior treatment for their prostate cancer. Results from those cohorts showed, respectively, PSA response rates of 26% and 31% and overall response rates of 20% and 14%.

The drugmaker did not disclose in its Thursday statement results from the Zytiga cohort.

Merck’s newly announced Phase 3 studies will test Keytruda in combination with Lynparza, Xtandi and chemotherapy. These pivotal tests will evaluate overall survival as a co-primary endpoint.

Merck wasn’t alone in rolling out fresh mCRPC data at this week’s American Society of Clinical Oncology’s Genitourinary Cancers Symposium.

Johnson & Johnson’s Janssen is set to present data Thursday on mCRPC patients treated with the PARP inhibitor Zejula (niraparib) in a Phase 2 study. That trial, for patients who also had DNA-repair pathway defects, found about 40% of patients treated daily with Zejula showed an objective response.

Additionally, Janssen has started a Phase 3 trial pairing Zejula with Zytiga and prednisone in metastatic prostate cancer and also has an ongoing Phase 2 trial of Zejula combinations in mCRPC.

Janssen holds exclusive rights to Zejula in prostate cancer through a licensing deal in 2016. The PARP inhibitor was developed by Tesaro, a company that was bought last December by GlaxoSmithKline for $5.1 billion.