Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)

Official Title

A Randomized, Double-Blind, Phase III Study of Pembrolizumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy for the Treatment of High-Risk Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (KEYNOTE-756)

Summary:

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.

The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.

Trial Description

Primary Outcome:

• Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
• Event-Free Survival (EFS)

Secondary Outcome:

• Overall Survival (OS)
• pCR Rate Using the Definition of ypT0ypN0
• pCR Rate Using the Definition of ypT0/Tis
• pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1
• EFS in Participants With a CPS ≥1
• OS in Participants With a CPS ≥1
• Number of Participants Experiencing an Adverse Event (AE)
• Number of Participants Experiencing a Serious Adverse Event (SAE)
• Number of Participants Experiencing an Immune-related AE (irAE)
• Number of Study Treatment Discontinuations Due to AEs
• Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score
• Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) Score

Study participants will receive 8 cycles of neoadjuvant study treatment and then will undergo surgery for their breast cancer. After surgery, participants will receive 9 cycles of study treatment and up to 10 years of variable endocrine therapy. Each cycle is 21 days long.

View this trial on ClinicalTrials.gov