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Merck Announces Success in Phase 3 KEYNOTE-522 Trial for High-Risk Early-Stage Triple Negative Breast Cancer (TNBC) | iPharmaCenter

KEYTRUDA (pembrolizumab) achieves milestone as first immunotherapy to significantly enhance overall survival in high-risk early-stage TNBC when combined with chemotherapy before surgery and as a solo treatment post-surgery.

Merck has revealed that its Phase 3 KEYNOTE-522 trial, which assesses the efficacy of KEYTRUDA, an anti-PD-1 therapy, in combination with chemotherapy as a pre-operative (neoadjuvant) treatment followed by solo administration post-surgery (adjuvant) for patients with high-risk early-stage triple-negative breast cancer (TNBC), has successfully met its overall survival (OS) endpoint. An independent Data Monitoring Committee conducted a pre-specified interim analysis, confirming that KEYTRUDA provided a statistically and clinically significant improvement in OS compared to pre-operative chemotherapy alone. The safety profile remained consistent with previous studies, and no new safety issues were identified. The findings will be presented at a forthcoming medical conference and communicated to regulatory bodies.

KEYNOTE-522 is the fourth trial to demonstrate an OS benefit with a KEYTRUDA-based regimen in early-stage cancers, following similar successes in KEYNOTE-A18 for cervical cancer, KEYNOTE-671 for non-small cell lung cancer, and KEYNOTE-564 for renal cell carcinoma.

In the United States, KEYTRUDA is approved for two indications in TNBC: for high-risk early-stage TNBC in combination with chemotherapy as a neoadjuvant treatment followed by adjuvant monotherapy post-surgery, and in combination with chemotherapy for locally recurrent unresectable or metastatic TNBC with tumors expressing PD-L1 (CPS ≥10) as confirmed by an FDA-approved test.

Merck is conducting an extensive clinical development program across various breast cancer subtypes. This includes:

  • KEYNOTE-242: Evaluating KEYTRUDA as adjuvant therapy in TNBC patients with residual disease.

  • KEYNOTE-756: Assessing KEYTRUDA plus chemotherapy in high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.

  • TroFuse-010: Comparing KEYTRUDA plus sacituzumab govitecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate developed with Kelun-Biotech, against sac-TMT alone and physician’s choice in patients with unresectable locally advanced or metastatic ER+/HER2- breast cancer.

  • TroFuse-012: Investigating KEYTRUDA plus sac-TMT versus physician’s choice in TNBC patients who received KEYTRUDA-based neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery.

About the KEYNOTE-522 Trial

KEYNOTE-522 (NCT03036488) is a randomized, double-blind Phase 3 study. It focuses on two primary endpoints: pathological complete response (pCR) rate, defined as the absence of invasive cancer in the breast and lymph nodes at surgery, and event-free survival (EFS), defined as the time until disease progression that prevents surgery, local/distant recurrence, second primary cancer, or death from any cause.

A crucial secondary endpoint is overall survival (OS). The trial involved 1,174 patients randomly assigned in a 2:1 ratio to receive either:

  1. KEYTRUDA Regimen: KEYTRUDA plus chemotherapy (paclitaxel and carboplatin), followed by KEYTRUDA plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy before surgery, and then KEYTRUDA monotherapy as adjuvant therapy post-surgery (n=784).

  2. Chemotherapy-Placebo Regimen: Placebo plus chemotherapy (paclitaxel and carboplatin), followed by placebo plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy before surgery, and then placebo monotherapy as adjuvant therapy post-surgery (n=390).

About Triple-Negative Breast Cancer (TNBC)

Triple-negative breast cancer is the most aggressive subtype of breast cancer, characterized by a high risk of recurrence within the first five years after diagnosis and generally worse outcomes compared to other breast cancer types. TNBC accounts for approximately 10-15% of all breast cancer cases. Unlike other breast cancers that may express estrogen receptors, progesterone receptors, or HER2, TNBC lacks these receptors. This cancer subtype is more prevalent in individuals under 40, Black women, and those with BRCA1 mutations.


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