A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)

Phase 3RecruitingNCT06966700

Merck Sharp & Dohme LLC2,400 enrolled

Overview

Researchers are looking for new ways to treat types of breast cancer that are both: * High-risk, which means the cancer may have a higher chance of getting worse or coming back after treatment * Early-stage, which means the cancer is in the breast or the lymph nodes around the breast The 2 types of breast cancer in this study are triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. These cancers have zero or a low amount of a protein called HER2 and other proteins that attach to the hormones estrogen or progesterone. Sacituzumab tirumotecan (also known as sac-TMT or MK-2870), the study medicine, is a type of targeted therapy. A targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. The main goals of this study are to learn if people who receive sac-TMT, pembrolizumab, and chemotherapy: * Have fewer cancer cells found in the tumors and lymph nodes removed during surgery compared to those who receive only pembrolizumab and chemotherapy * Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

2,400

Conditions

Breast Neoplasms Triple Negative Breast Neoplasms

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has previously untreated high-risk, early-stage, non-metastatic (M0) breast cancer (BC), defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per AJCC 8th edition criteria as assessed by the investigator based on radiological and/or clinical assessment: * cT1c, N1-N2 * cT2, N0-N2 * cT3, N0-N2 * cT4a-d, N0-N2 * The participant must have a centrally confirmed diagnosis of BC that is triple-negative or HR-low+/HER2- (defined as estrogen receptor (ER)-low+ expression in 1% to 10% cells and HER2-), as by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. * Provides a core needle biopsy from the primary breast tumor at screening to the central laboratory. * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 28 days before treatment randomization. * Demonstrates adequate organ function. Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Metastatic (Stage IV) breast cancer or clinical node stage 3 (cN3) nodal involvement * Has received any prior treatment, including radiation, systemic therapy,and/or definitive surgery for currently diagnosed breast cancer * Has undergone excisional biopsy of the primary tumor, axillary lymph node dissection, and/or axillary sentinel lymph node biopsy prior to study treatment. * Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization. * Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137). * Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC). * Received prior treatment with a topoisomerase I inhibitor-containing ADC. * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Known additional malignancy that is progressing or has required active treatment within the past 5 years. * Uncontrolled systemic disease. * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Outcomes

Primary Outcomes

Percentage of Participants with Pathological Complete Response (pCR) at the Time of Definitive Surgery

pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.

Time frame: Up to approximately 30 weeks

Event-Free Survival (EFS)

EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first.

Time frame: Up to approximately 92 months

Secondary Outcomes

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 115 months

Percentage of Participants with pCR with No Ductal Carcinoma in Situ (pCR-no DCIS) at the Time of Definitive Surgery

pCR-no ductal carcinoma in situ (DCIS) (ypT0 ypN0) is defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.

Time frame: Up to approximately 30 weeks

Percentage of Participants with pCR at the Time of Definitive Surgery (High-risk, early-stage, TNBC subset)

Time frame: Up to approximately 30 weeks

Event-Free Survival (EFS) (High-risk, early-stage, TNBC subset)

EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first. The EFS will be presented for the subset of participants who enrolled with high-risk, early-stage, TNBC.

Time frame: Up to approximately 92 months

Overall Survival (OS) (High-risk, early-stage, TNBC subset)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 115 months

Distant Progression or Distant Recurrence-Free Survival (DPDRFS)

DPDRFS is defined as the time from randomization to first distant progression or distant recurrence event as assessed by investigator, or death due to any cause, whichever occurs first.

Time frame: Up to approximately 92 months

Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status-Quality of Life Score

The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to Item 30 (""How would you rate your overall quality of life during the past week?") is scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher value indicates a better level of function. The change from baseline in EORTC QLQ-C30 Item 30 score will be reported.