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

Description
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

Objective
Primary Objective:
1. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy with respect to rate of pCR (ypT0/Tis ypN0) at the time of surgery, as
assessed by local pathologist in all participants.

2. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy and pembrolizumab with optional adjuvant TPC with respect to EFS as
assessed by investigator in all participants.

Secondary Objectives:
1. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy and pembrolizumab with optional adjuvant TPC with respect to OS in all
participants.

2. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy with respect to rate of pCR-no DCIS (ypT0 ypN0) at the time of surgery, as assessed by local pathologist in all participants.

3. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy with respect to rate of pCR (ypT0/Tis ypN0) at the time of surgery, as assessed by local pathologist in all participants with high-risk, early-stage, TNBC.

4. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy and pembrolizumab with optional adjuvant TPC with respect to EFS as assessed by investigator in all participants with high-risk, early-stage, TNBC.

5. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy and pembrolizumab with optional adjuvant TPC with respect to OS in participants with high-risk, early-stage, TNBC.

6. To compare sac-TMT followed by carboplatin/paclitaxel versus chemotherapy, both in combination with pembrolizumab as neoadjuvant therapy and pembrolizumab with optional adjuvant TPC with respect to DPDRFS in all participants.

7. To evaluate mean change from baseline in HRQoL assessments using EORTC QLQ-C30 and EORTC QLQ-BR42 questionnaires in both arms.

8. To evaluate the safety and tolerability of sac- TMT plus pembrolizumab followed by carboplatin/paclitaxel plus pembrolizumab.

Treatment 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

Key Eligibility 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.

Applicable Disease Sites
Breast

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital