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)

• ClinicalTrials.gov Identifier: NCT06312176
• Recruitment Status: Recruiting
• First Posted: March 15, 2024
• Last Update Posted: May 7, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: March 7, 2024
• First Posted Date: March 15, 2024
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: April 14, 2024
• Estimated Primary Completion Date: July 11, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 5, 2024)

Progression-Free Survival (PFS) ( sacituzumab tirumotecan versus treatment of physician's choice [TPC]; pembrolizumab + sacituzumab tirumotecan versus TPC) [ Time Frame: Up to ~38 months ]

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.

Original Primary Outcome Measures (submitted: March 7, 2024)

Progression-Free Survival (PFS) (MK-2870 versus treatment of physician's choice [TPC]; MK-2870 + pembrolizumab versus TPC) [ Time Frame: Up to ~38 months ]

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.

Current Secondary Outcome Measures (submitted: May 5, 2024)

• Overall Survival (OS) [ Time Frame: Up to ~77 months ]
  OS is defined as the time from randomization to death due to any cause.
• Progression-Free Survival (PFS) (pembrolizumab + sacituzumab tirumotecan + versus sacituzumab tirumotecan) [ Time Frame: Up to ~57 months ]
  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.
• Objective Response Rate (ORR) [ Time Frame: Up to ~57 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to ~57 months ]
  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.
• 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) [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in physical functioning score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in emotional functioning score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in fatigue score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in diarrhea score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Time to first Deterioration (TTD) in global health status/quality of life scores, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in physical functioning score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in emotional functioning score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in fatigue score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in diarrhea score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• Number of participants who experience one or more adverse events (AEs) [ Time Frame: Up to ~77 months ]
  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.
• Number of participants who discontinue study treatment due to an AE [ Time Frame: Up to ~77 months ]
  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.

Original Secondary Outcome Measures (submitted: March 7, 2024)

• Overall Survival (OS) [ Time Frame: Up to ~77 months ]
  OS is defined as the time from randomization to death due to any cause.
• Progression-Free Survival (PFS) (MK-2870 + pembrolizumab versus MK-2870) [ Time Frame: Up to ~57 months ]
  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.
• Objective Response Rate (ORR) [ Time Frame: Up to ~57 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to ~57 months ]
  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.
• 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) [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in physical functioning score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in emotional functioning score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in fatigue score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Change from baseline in diarrhea score, on the EORTC QLQ-C30 [ Time Frame: Baseline and up to ~77 months ]
  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.
• Time to first Deterioration (TTD) in global health status/quality of life scores, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in physical functioning score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in emotional functioning score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in fatigue score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• TTD in diarrhea score, on the EORTC QLQ-C30 [ Time Frame: Up to ~77 months ]
  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.
• Number of participants who experience one or more adverse events (AEs) [ Time Frame: Up to ~77 months ]
  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.
• Number of participants who discontinue study treatment due to an AE [ Time Frame: Up to ~77 months ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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

Brief 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Neoplasms

Intervention

• Drug: Sacituzumab tirumotecan
  IV infusion
  Other Name: MK-2870
• Biological: Pembrolizumab
  IV infusion
  Other Names:

  • MK-3475
  • KEYTRUDA®
• Drug: Paclitaxel
  IV infusion
  Other Name: TAXOL®
• Drug: Nab-paclitaxel
  IV infusion
  Other Name: ABRAXANE®
• Drug: Capecitabine
  oral tablet
  Other Name: XELODA®
• Drug: Liposomal doxorubicin
  IV infusion
  Other Name: DOXIL®

Study Arms

• Experimental: Arm A: Sacituzumab tirumotecan
  Participants receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.
  Intervention: Drug: Sacituzumab tirumotecan
• Experimental: Arm B:Pembrolizumab + Sacituzumab tirumotecan
  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).
  Interventions:

  • Drug: Sacituzumab tirumotecan
  • Biological: Pembrolizumab
• Active Comparator: Arm C: Treatment of Physician's Choice (TPC)
  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.
  Interventions:

  • Drug: Paclitaxel
  • Drug: Nab-paclitaxel
  • Drug: Capecitabine
  • Drug: Liposomal doxorubicin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 7, 2024): 1200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 12, 2031
• Estimated Primary Completion Date: July 11, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Israel, Taiwan, United States

Administrative Information

• NCT Number: NCT06312176
• Other Study ID Numbers: 2870-010; MK-2870-010 ( Other Identifier: Merck ); 2023-504918-29 ( Registry Identifier: EU CT ); U1111-1289-8119 ( Other Identifier: UTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2024