Title
An Open-label, Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination with Pembrolizumab Versus Treatment of Physician's Choice in Participants with HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer

Description
An Open-label, Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer

Objective
Primary Objectives:
1. To compare MK-2870 to TPC with respect to PFS per RECIST 1.1 as assessed by BICR in all participants.
2. To compare MK-2870 plus pembrolizumab to TPC with respect to PFS per RECIST 1.1 as assessed by BICR in all participants.

Secondary Objectives:
1. To compare MK-2870 to TPC with respect to OS in all participants.
2. To compare MK-2870 plus pembrolizumab to TPC with respect to OS in all participants.
3. To compare MK-2870 plus pembrolizumab to MK-2870 with respect to PFS per RECIST 1.1 as assessed by BICR in all participants.
4. To compare MK-2870 plus pembrolizumab to MK-2870 with respect to OS in all participants.
5. To compare MK-2870 to TPC with respect to ORR per RECIST 1.1 as assessed by BICR in all participants.
6. To compare MK-2870 plus pembrolizumab to TPC with respect to ORR per RECIST 1.1 as assessed by BICR in all participants.
7. To evaluate MK-2870 to TPC with respect to DOR per RECIST 1.1 as assessed by BICR in all participants.
8. To evaluate MK-2870 plus pembrolizumab to TPC with respect to DOR per RECIST 1.1 as assessed by BICR in all participants.
9. To compare MK-2870 to TPC with respect to mean change from baseline in HRQoL using the EORTC QLQ-C30 in all participants.
10. To compare MK-2870 to TPC with respect to TTD in HRQoL using the EORTC QLQ-C30 in all participants.
11. To compare MK-2870 plus pembrolizumab to TPC with respect to mean change from baseline in HRQoL using the EORTC QLQ-C30 in all participants.
12. To compare MK-2870 plus pembrolizumab to TPC with respect to TTD in HRQoL using the EORTC QLQ-C30 in all participants.
13. To evaluate the safety and tolerability of MK-2870, MK-2870 plus pembrolizumab, and chemotherapy.

Treatment The purpose of this study is to compare sacituzumab tirumotecan as a single agent, and in combination with pembrolizumab, versus Treatment of Physician's Choice (TPC) in participants with hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) unresectable locally advanced, or metastatic, breast cancer.

The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.

Key Eligibility Inclusion Criteria:

Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer

Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor

Is a chemotherapy candidate

Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization

Has adequate organ function

Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy

Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load

Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Has breast cancer amenable to treatment with curative intent

Has experienced an early recurrence (<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment

Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications

Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer

Active autoimmune disease that has required systemic treatment in the past 2 years

History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease

Has an active infection requiring systemic therapy

Applicable Disease Sites
Breast

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