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)

Breast Neoplasms Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06312176
• Other study ID #: 2870-010
• Secondary ID: MK-2870-0102023-
• Status: Recruiting
• Phase: Phase 3
• Start date: April 14, 2024
• Est. completion date: April 12, 2031

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: April 12, 2031
• Est. primary completion date: July 11, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Sacituzumab tirumotecan
IV infusion

Biological:
• Pembrolizumab
IV infusion

Drug:
• Paclitaxel
IV infusion
• Nab-paclitaxel
IV infusion
• Capecitabine
oral tablet
• Liposomal doxorubicin
IV infusion

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus-Oncology Division ( Site 1452)	Haifa
Israel	Rabin Medical Center ( Site 1453)	Petah Tikva
Taiwan	National Cheng Kung University Hospital-Surgery ( Site 2411)	Tainan
United States	Hematology Oncology Associates of Rockland ( Site 0054)	Nyack	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Israel,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) ( sacituzumab tirumotecan versus treatment of physician's choice [TPC]; pembrolizumab + sacituzumab tirumotecan versus TPC)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.	Up to ~38 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~77 months
Secondary	Progression-Free Survival (PFS) (pembrolizumab + sacituzumab tirumotecan + versus sacituzumab tirumotecan)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.	Up to ~57 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to ~57 months
Secondary	Duration of Response (DOR)	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to ~57 months
Secondary	Change from baseline in global health status/quality of life scores, on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status.	Baseline and up to ~77 months
Secondary	Change from baseline in physical functioning score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of physical functioning.	Baseline and up to ~77 months
Secondary	Change from baseline in emotional functioning score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of emotional functioning.	Baseline and up to ~77 months
Secondary	Change from baseline in fatigue score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their fatigue are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function.	Baseline and up to ~77 months
Secondary	Change from baseline in diarrhea score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Have you had diarrhea?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function.	Baseline and up to ~77 months
Secondary	Time to first Deterioration (TTD) in global health status/quality of life scores, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. TTD is defined as the time from baseline to the first onset of a 10-point deterioration from baseline in global health status/quality of life combined score.	Up to ~77 months
Secondary	TTD in physical functioning score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of physical functioning. TTD is defined as the time from baseline to the first onset of a 10-point deterioration from baseline in the physical functioning score.	Up to ~77 months
Secondary	TTD in emotional functioning score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their emotional functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of emotional functioning. TD is defined as the time from baseline to the first onset of a 10-point deterioration from baseline in the emotional functioning score.	Up to ~77 months
Secondary	TTD in fatigue score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to questions about their fatigue are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function. TTD is defined as the time from baseline to the first onset of a 10-point deterioration from baseline in the fatigue score.	Up to ~77 months
Secondary	TTD in diarrhea score, on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question about their diarrhea are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better level of function. TTD is defined as the time from baseline to the first onset of a 10-point deterioration from baseline in the diarrhea score.	Up to ~77 months
Secondary	Number of participants who experience one or more adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to ~77 months
Secondary	Number of participants who discontinue study treatment due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to ~77 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary