Merck's Phase 3 Trial Achieves Survival Endpoint in High-Risk Early TNBC

Merck has announced that their Phase 3 KEYNOTE-522 trial has resulted in a statistically significant improvement in overall survival (OS) for patients with high-risk early-stage triple-negative breast cancer (TNBC) when treated with KEYTRUDA® (pembrolizumab) in combination with chemotherapy as a neoadjuvant therapy and continued as a monotherapy post-surgery. This milestone is notable as it marks the first time an immunotherapy regimen has outperformed chemotherapy alone in this patient group. The trial’s interim analysis, conducted by an independent Data Monitoring Committee, confirmed the safety profile of KEYTRUDA, which was consistent with previous studies, with no new safety concerns. The results will be presented at a forthcoming medical meeting and shared with regulatory bodies.

The KEYNOTE-522 trial is a randomized, double-blind Phase 3 study that enrolled 1,174 patients, who were divided into two groups in a 2:1 ratio. One group received KEYTRUDA plus chemotherapy (paclitaxel and carboplatin), followed by another round of KEYTRUDA plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as pre-operative treatment, and continued with KEYTRUDA monotherapy after surgery. The control group received a placebo with the same chemotherapy regimen. The trial’s primary endpoints included the pathological complete response rate (pCR) and event-free survival, with OS being a key secondary endpoint. The KEYTRUDA regimen demonstrated a significant improvement in OS compared to the control group.

Dr. Gursel Aktan, Vice President of Global Clinical Development at Merck Research Laboratories, highlighted the significance of this achievement, noting that it builds on the positive data from pathological complete response and event-free survival results previously reported. This success not only enhances treatment modalities for high-risk early-stage TNBC but also adds to the growing evidence of KEYTRUDA’s efficacy in various early-stage cancers, such as cervical cancer (KEYNOTE-A18), non-small cell lung cancer (KEYNOTE-671), and renal cell carcinoma (KEYNOTE-564).

KEYTRUDA is already approved in the U.S. for two TNBC indications: as neoadjuvant therapy in combination with chemotherapy for high-risk early-stage patients, continued as adjuvant monotherapy post-surgery, and in combination with chemotherapy for locally recurrent unresectable or metastatic TNBC expressing PD-L1 (CPS ≥10). Merck is also conducting extensive research across multiple subtypes of breast cancer, including ongoing Phase 3 trials like KEYNOTE-242, KEYNOTE-756, TroFuse-010, and TroFuse-012, evaluating various combinations and monotherapies involving KEYTRUDA.

Triple-negative breast cancer, making up 10-15% of breast cancer cases, is particularly aggressive and has higher recurrence risks within the first five years post-diagnosis, compared to other breast cancer types. It is commonly diagnosed in younger women, Black women, and those with BRCA1 mutations. TNBC is characterized by the absence of estrogen receptors, progesterone receptors, and HER2 protein expression.

Merck’s broader research initiatives aim to improve outcomes in breast and gynecologic cancers, with a robust clinical development program encompassing over 20 Phase 3 studies. Their efforts also extend to investigating KEYTRUDA in earlier cancer stages and exploring potential new combinations and formulations. Their comprehensive approach underscores the importance of early-stage cancer detection and treatment, which can significantly enhance the chances of long-term survival.

KEYTRUDA, an anti-PD-1 therapy, enhances the body's immune system to detect and fight tumor cells. It is currently being studied in over 1,600 trials across various cancers and treatment settings, aiming to understand its role better and identify biomarkers that predict patient response.

In summary, the successful results from the KEYNOTE-522 trial mark a significant advancement in treating high-risk early-stage TNBC, highlighting the potential of immunotherapy in oncology and reinforcing Merck’s commitment to improving cancer outcomes.