Clinical trial NCT06841354: 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)
Official title: A Phase 3, Randomized, Open-label Study Comparing Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as a Monotherapy and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With Previously Untreated Locally Recurrent Unresectable or Metastatic Triple-Negative Breast Cancer Expressing PD-L1 at CPS Less Than 10 (TroFuse-011)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Triple Negative Breast Neoplasms
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Antibody-drug conjugate (ADC)
Trophoblast cell-surface antigen 2 (TROP2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-02-24
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 TNBC
* 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 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 TNBC
* Has Grade ≥2 peripheral neuropathy
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or 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

Primary outcomes:
measure: Progression-Free Survival (PFS) (sac-TMT versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus TPC)
timeFrame: Up to ~37 months
measure: Overall Survival (OS) (sac-TMT versus TPC)
timeFrame: Up to ~61 months
Secondary outcomes:
measure: Overall Survival (OS) (sac-TMT plus pembrolizumab versus treatment of physician's choice (TPC); sac-TMT plus pembrolizumab versus sac-TMT)
timeFrame: Up to ~61 months
measure: Progression-Free Survival (PFS) (sac-TMT plus pembrolizumab versus sac-TMT)
timeFrame: Up to ~37 months
measure: Objective Response Rate (ORR) (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)
timeFrame: Up to ~37 months
measure: Duration of Response (DOR)
timeFrame: Up to ~37 months
measure: 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)
timeFrame: Baseline and up to ~61 months
measure: Change from baseline in physical functioning score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)
timeFrame: Baseline and up to ~61 months
measure: Change from baseline in emotional functioning score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)
timeFrame: Baseline and up to ~61 months
measure: Change from baseline in fatigue score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)
timeFrame: Baseline and up to ~61 months
measure: Change from baseline in diarrhea score, on the EORTC QLQ-C30 (sac-TMT versus TPC; sac-TMT plus pembrolizumab versus TPC)
timeFrame: Baseline and up to ~61 months
measure: Number of participants who experience one or more adverse events (AEs)
timeFrame: Up to ~61 months
measure: Number of participants who discontinue study treatment due to an AE
timeFrame: Up to ~61 months
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers ( Site 0036)
state: Arizona
city: New Haven
country: United States
facility: Yale New Haven Hospital ( Site 0001)
state: Connecticut
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada ( Site 0015)
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center ( Site 0005)
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants Ltd. ( Site 0019)
state: New Mexico
city: Rosario
country: Argentina
facility: Fundacion Estudios Clinicos ( Site 2405)
state: Santa Fe
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 3700)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 3704)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 3702)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 3701)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 3703)
city: Tsu
country: Japan
facility: Mie University Hospital ( Site 5109)
state: Mie
city: Shinagawa
country: Japan
facility: Showa Medical University Hospital ( Site 5103)
state: Tokyo
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 5204)
state: Kyonggi-do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital ( Site 5205)
state: Kyongsangbuk-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 5200)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 5201)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 5203)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital ( Site 5303)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 5304)
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital ( Site 5301)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: