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

Merck Sharp & Dohme (MSD)

Status and phase: Begins enrollment this month; Phase 3

Conditions: Triple Negative Breast Neoplasms; Breast Neoplasms; HR Low-Positive/HER2-Negative Breast Neoplasms

Treatments: Drug: Carboplatin; Drug: Cyclophosphamide; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Capecitabine; Biological: Sacituzumab tirumotecan; Drug: Rescue Medication; Drug: Olaparib; Drug: Epirubicin; Drug: Doxorubicin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06966700

2870-032

Details and patient eligibility

About

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

Enrollment: 2,400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

2,400 participants in 2 patient groups

sac-TMT

Experimental group

Description:

Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m\^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m\^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m\^2 IV infusion Q3W/Q2W for 4 doses.

Treatment:

Drug: Epirubicin

Drug: Doxorubicin

Drug: Olaparib

Drug: Rescue Medication

Biological: Sacituzumab tirumotecan

Drug: Capecitabine

Drug: Paclitaxel

Drug: Cyclophosphamide

Biological: Pembrolizumab

Drug: Carboplatin

Chemotherapy

Active Comparator group

Description:

Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m\^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m\^2 Q3W and either doxorubicin 60 mg/m\^2 Q3W or epirubicin 90 mg/m\^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m\^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.

Treatment:

Drug: Epirubicin

Drug: Doxorubicin

Drug: Olaparib

Drug: Rescue Medication

Drug: Capecitabine

Drug: Paclitaxel

Drug: Cyclophosphamide

Biological: Pembrolizumab

Drug: Carboplatin