Clinical trial NCT06966700: A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)
Official title: A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Sac-TMT (Sacituzumab Tirumotecan, MK-2870) Followed by Carboplatin/Paclitaxel vs Chemotherapy, Both in Combination With Pembrolizumab as Neoadjuvant Therapy for High-Risk, Early-Stage, Triple-Negative Breast Cancer or Hormone Receptor-low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Breast Neoplasms
Triple Negative Breast Neoplasms
HR Low-Positive/HER2-Negative Breast Neoplasms
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-05-13
Enrollment: 2400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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 epidermal growth factor 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 10 days of treatment initiation.
* 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.

Primary outcomes:
measure: Percentage of Participants with Pathological Complete Response (pCR) at the Time of Definitive Surgery
timeFrame: Up to approximately 30 weeks
measure: Event-Free Survival (EFS)
timeFrame: Up to approximately 92 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 115 months
measure: Percentage of Participants with pCR with No Ductal Carcinoma in Situ (pCR-no DCIS) at the Time of Definitive Surgery
timeFrame: Up to approximately 30 weeks
measure: Percentage of Participants with pCR at the Time of Definitive Surgery (High-risk, early-stage, TNBC subset)
timeFrame: Up to approximately 30 weeks
measure: Event-Free Survival (EFS) (High-risk, early-stage, TNBC subset)
timeFrame: Up to approximately 92 months
measure: Overall Survival (OS) (High-risk, early-stage, TNBC subset)
timeFrame: Up to approximately 115 months
measure: Distant Progression or Distant Recurrence-Free Survival (DPDRFS)
timeFrame: Up to approximately 92 months
measure: 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
timeFrame: Baseline and up to approximately 3 years
measure: Change from Baseline in EORTC QLQ-C30 Physical Functioning Score
timeFrame: Baseline and up to approximately 3 years
measure: Change from Baseline in EORTC QLQ-C30 Role Functioning Score
timeFrame: Baseline and up to approximately 3 years
measure: Change from Baseline in EORTC QLQ-C30 Fatigue Score
timeFrame: Baseline and up to approximately 3 years
measure: Change from Baseline in EORTC QLQ Breast Cancer 42 (BR42) Systemic Therapy Side Effects Score
timeFrame: Baseline and up to approximately 3 years
measure: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 67 weeks
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 54 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: