Merck Announces Ups and Downs Involving Blockbuster Keytruda

Merck_Kena Betancur/Getty Images

Kena Betancur/Getty Images

Sydney, Australia-based Imugene announced a clinical trial collaboration and supply deal with Merck.They will evaluate Imugene’s HER-Vaxx in combination with Merck’s blockbuster anti-PD-1 checkpoint inhibitor Keytruda (pembrolizumab) in HER-2 positive gastric cancer. HER-Vaxx is a B-cell activating immunotherapy.

The Phase II nextHERIZON trial will evaluate HER-vaxx in combination with chemotherapy or Keytruda in patients with metastatic HER-2/neu over-expressing gastric or gastroesophageal junction adenocarcinomas who have previously progressed on trastuzumab. The primary endpoints are safety and response rate.

Imugene will sponsor and fund the study. Merck will provide Keytruda for the duration of the trial.

“Imugene is excited to announce this collaboration with MSD [Merck], one of the world’s leading immuno-oncology companies,” said Leslie Chong, Imugene’s managing director and chief executive officer. “HER-Vaxx has already shown a tolerable safety profile and encouraging efficacy in patients with metastatic HER-2 positive gastric cancer, and we look forward to further evaluating HER-Vaxx with pembrolizumab in a relapsed/refractory metastatic setting.”

Merck also announced that it is halting its Phase III KEYLYNK-010 trial of Keytruda in combination with Merck and AstraZeneca’s Lynparza (olaparib), a PARP inhibitor, for patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after treatment with chemotherapy and either abiraterone acetate or enzalutamide. An independent Data Monitoring Committee (DMC) reviewed data from a planned interim analysis and reported the combination did not show an overall survival (OS) benefit, one of the trial’s dual primary endpoints, compared to the control arm of either abiraterone acetate or enzalutamide. 

Earlier, the company had evaluated the other dual primary endpoint, radiographic progression free survival (rPFS), which didn’t demonstrate improvement compared to the control arm either.

Merck has other clinical trials involving Keytruda in prostate cancer and more than 1,000 studies in other cancers with other drugs. These include the Phase II KEYNOTE-199 and -365 trials, the Phase III KEYNOTE-641, -921 and -911, and the Phase III PROpel trial. KEYLYNK-010 is only one of several studies of Keytruda plus Lynparza, which in addition to prostate cancer, is being evaluated in advanced lung cancer, ovarian cancer, triple-negative breast cancer, and solid tumors with specific biomarkers.

“There remains a significant unmet need for patients diagnosed with advanced prostate cancer, who have a poor prognosis after not responding to initial therapy,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Merck continues to evaluate the combination of Keytruda and Lynparza in a range of cancers, and to research other Keytruda-based combinations for patients with advanced prostate cancer. We are grateful to the patients, their families and the investigators who made this study possible.”

On March 11, the U.S. Food and Drug Administration approved Lynparza for adjuvant treatment of adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer patients who have been treated with neoadjuvant or adjuvant chemotherapy. The indication requires an FDA-approved companion diagnostic test.

The approval was built on data from the Phase III OlympiA trial. Its primary endpoint was invasive disease-free survival (IDFS), which demonstrated a statistically significant improvement, decreasing the risk of invasive breast cancer recurrences, second cancer or death by 42%.

Baynes said at the time, “For patients with germline BRCA-mutated, HER2-negative high-risk early breast cancer, who often present with more aggressive disease, today’s approval is an important step forward. Compared to placebo, Lynparza as adjuvant treatment offers these patients the potential to live longer without their cancer recurring. We thank the patients, caregivers and healthcare providers for their participation in the OlympiA trial.”

Back to news