Merck and AstraZeneca Discontinue Keytruda-Lynparza Combination Therapy in Prostate Cancer Following Phase 3 Setback

Compiled by Tom Li

Recently, the combination therapy of Merck & Co., Inc.'s blockbuster Keytruda and AstraZeneca's Lynparza failed to outperform the commonly used anti-androgen therapy in previously treated patients with metastatic castration-resistant prostate cancer (mCRPC). The company then announced the termination of the development of the Keytruda-Lynparza combination therapy.

Trial results show that, compared with Johnson & Johnson's Zytiga or Pfizer's Xtandi, the Keytruda-Lynparza combination therapy failed to further extend the lives of mCRPC patients and also couldn't halt tumor progression. Even worse, MSD’s combination therapy increased the incidence of grade 3-5 drug-related serious adverse effects in mCRPC patients. Following the interim analysis results of the Phase 3 Keylynk-010 trial ending in a disastrous failure, MSD has decided to follow the recommendation of the independent data monitoring committee to terminate the development trial of the combination therapy as soon as possible.

It is worth noting that the failure of this trial result is inevitably surprising. Keytruda and Lynparza have both been regarded as blockbusters in their respective fields. Keytruda is a representative drug in the PD-1 field, while Lynparza is the world's best-selling PARP inhibitor. In addition, Lynparza alone has already been approved for use in mCRPC patients with homologous recombination repair gene mutations who experienced disease progression after prior treatment with Xtandi or Zytiga, based on clinical trial data.

Despite the failure of this combination therapy trial for prostate cancer, Merck & Co., Inc. still has several other clinical trials involving Keytruda for the treatment of prostate cancer, as well as over 1,000 studies on combination therapies with other drugs for various cancers. These include Phase II KEYNOTE-199 and KEYNOTE-365 trials, Phase III KEYNOTE-641, KEYNOTE-921, and the Phase III PROpel trial, among others.

Besides, MSD recently announced a clinical trial collaboration and supply agreement with Imugene, headquartered in Sydney, Australia. The two parties will test the effect of Imugene's HER-Vaxx combined with Keytruda in HER-2 positive gastric cancer. The Phase II next HERIZON trial will evaluate the efficacy of HER-vaxx in combination with chemotherapy or Keytruda for patients with metastatic HER-2/neu overexpressing gastric or gastroesophageal junction adenocarcinoma who have previously received trastuzumab treatment. The primary endpoints of the trial are the safety and response rate of the combination therapy. Imugene will sponsor the cost required for the study, while MSD will be responsible for providing Keytruda during the trial period.

Meanwhile, Keytruda's main competitor, Bristol-Myers Squibb's Opdivo, has also partnered with Clovis Oncology's Rubraca to develop a combination therapy. Recently published results from a Phase 2 trial named CheckMate 9KD showed that the combination of Opdivo and Rubraca provided survival benefits for patients with metastatic castration-resistant prostate cancer (mCRPC) who have homologous recombination deficiency and have not received chemotherapy. Additionally, AstraZeneca itself has been actively researching the efficacy of the combination therapy of Lynparza and Imfinzi. For example, the Phase 3 Duo-O trial is evaluating the treatment effects of Lynparza, Imfinzi, and Roche’s Avastin on ovarian cancer.

Reference Source:

1、In rare flop, Merck calls it quits on Keytruda-Lynparza combo in prostate cancer

2、Merck Announces Ups and Downs Involving Blockbuster Keytruda