A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Breast Neoplasms

Treatments: Drug: Liposomal doxorubicin; Drug: Sacituzumab tirumotecan; Biological: Pembrolizumab; Drug: Nab-paclitaxel; Drug: Capecitabine; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT06312176

2023-504918-29 (Registry Identifier)

2870-010

MK-2870-010 (Other Identifier)

U1111-1289-8119 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,200 participants in 3 patient groups

Arm A: Sacituzumab tirumotecan

Experimental group

Description:

Participants receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.

Treatment:

Drug: Sacituzumab tirumotecan

Arm B:Pembrolizumab + Sacituzumab tirumotecan

Experimental group

Description:

Participants receive 4 mg/kg of sacituzumab tirumotecan Q2W via IV infusion until progressive disease or discontinuation PLUS 400 mg of pembrolizumab once every 6 weeks (Q6W) via IV infusion for up to 18 administrations (up to \~2 years).

Treatment:

Biological: Pembrolizumab

Drug: Sacituzumab tirumotecan

Arm C: Treatment of Physician's Choice (TPC)

Active Comparator group

Description:

At the physician's discretion, participants receive chemotherapy of 80 mg/m\^2 of paclitaxel once every week (Q1W) via IV infusion OR 90 mg/m\^2 of paclitaxel once every 4 weeks (Q4W) via IV infusion OR 100 mg/m\^2 of nab-paclitaxel Q4W via IV infusion OR 1000 mg/m\^2 of capecitabine every 3 weeks (Q3W) orally OR 50 mg/m\^2 of liposomal doxorubicin once every 4 weeks (Q4W) via IV infusion, until progressive disease or discontinuation.

Treatment:

Drug: Paclitaxel

Drug: Capecitabine

Drug: Nab-paclitaxel

Drug: Liposomal doxorubicin