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)

Conditions

• Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab (K) — BIOLOGICAL
  IV infusion Q3W
• Placebo (P) — DRUG
  Normal saline or dextrose IV infusion Q3W
• Paclitaxel (X) — DRUG
  IV infusion QW
• Doxorubicin (A) — DRUG
  IV infusion either in Q2W or Q3W
• Epirubicin (E) — DRUG
  IV infusion either in Q2W or Q3W
• Cyclophosphamide (C) — DRUG
  IV infusion either in Q2W or Q3W
• Endocrine therapy — DRUG
  Variable endocrine therapy for up 10 years
• Radiation therapy — RADIATION
  Variable radiation therapy per local standard of care
• Surgery — PROCEDURE
  Surgery for breast cancer

Study Details

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.

Key Dates

First listed

Oct 30, 2018

Start date

Dec 27, 2018

Status verified

Jul 2025

Primary completion

Jan 24, 2031

Completion

Jan 24, 2031

Study Design

Enrollment

1,240 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Pembrolizumab+Chemotherapy (KX/KA[E]C)
  In the neoadjuvant setting, participants receive pembrolizumab (K) 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) + paclitaxel (X) 80 mg/m\^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by pembrolizumab 200 mg via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m\^2 or 100 mg/m\^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive pembrolizumab 200 mg via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.
• Placebo Comparator: Placebo+Chemotherapy (PX/PA[E]C)
  In the neoadjuvant setting, participants receive placebo (P; normal saline or dextrose) via IV infusion Q3W + paclitaxel (X) 80 mg/m\^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by placebo via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m\^2 or 100 mg/m\^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m\^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive placebo via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.

Primary Outcome Measure

Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 [ Time Frame: Up to approximately 7 months (Time of surgery) ]

Locations (45)

Find similar trials in Daphne, AL

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