A Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Triple-Negative Breast Cancer (MK-2870-011/TroFuse-011)

Phase 3RecruitingNCT06841354

Merck Sharp & Dohme LLC1,000 enrolled

Overview

Researchers want to know if sacituzumab tirumotecan given alone or with pembrolizumab can treat triple negative breast cancer (TNBC). The main goal of this study is to learn if people treated with sacituzumab tirumotecan alone or with pembrolizumab live longer overall or without the cancer growing or spreading compared to people treated with chemotherapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,000

Conditions

Triple Negative Breast Neoplasms

Interventions

Sacituzumab tirumotecanBIOLOGICAL

Rescue MedicationDRUG

Participants receive the following pre-medications before sacituzumab tirumotecan infusion: Histamine-1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion. Participants are also recommended to receive prophylactic steroid mouthwash (dexamethasone or equivalent).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has locally recurrent unresectable or metastatic TNBC that cannot be treated with curative intent * Has not received systemic treatment for locally recurrent unresectable or metastatic breast cancer * Participants previously treated for early-stage breast cancer must have completed all prior therapy for early-stage breast cancer with curative intent at least 6 months before the first disease recurrence * Is a candidate for treatment with pembrolizumab and one of the TPC options: paclitaxel or nab-paclitaxel or gemcitabine + carboplatin * Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline with the exception of alopecia or vitiligo. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has breast cancer amenable to treatment with curative intent * Has TNBC with evaluable tumor programmed death ligand 1 (PD-L1) expression at combined positive score (CPS) ≥10 * Has received prior systemic therapy for treatment of locally recurrent unresectable or metastatic breast cancer * Has Grade ≥2 peripheral neuropathy * Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing * Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease * Has skin only metastatic disease * Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications * Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has known additional malignancy that is progressing or has required active treatment within the past 5 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable * Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid (DNA)) and Hepatitis C virus (HCV) (defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection * History of stem cell/solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications

Locations (242)

USA Mitchell Cancer Institute ( Site 0090)

Mobile, Alabama, United States

RECRUITING

Ironwood Cancer & Research Centers ( Site 0036)

Chandler, Arizona, United States

RECRUITING

City of Hope ( Site 0097)

Duarte, California, United States

RECRUITING

City of Hope Lennar Foundation Cancer Center ( Site 0099)

Irvine, California, United States

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) (sac-TMT versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus TPC)

PFS is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. 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.

Time frame: Up to ~37 months

Overall Survival (OS) (sac-TMT versus TPC)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to ~61 months

Secondary Outcomes

Overall Survival (OS) (sac-TMT plus pembrolizumab versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus sac-TMT)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to ~61 months

Progression-Free Survival (PFS) (sac-TMT plus pembrolizumab versus sac-TMT)

PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. 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.

Time frame: Up to ~37 months

Objective Response Rate (ORR) (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)

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 RECIST 1.1 based on BICR.

Time frame: Up to ~37 months

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 RECIST 1.1 based on BICR, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death, whichever occurs first. 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.

Time frame: Up to ~37 months

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) (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)

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.