Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012)

Triple-Negative Breast Cancer Clinical Trial

Official title:

A Phase 3, Randomized, Open-label, Study to Compare the Efficacy and Safety of Adjuvant MK-2870 in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice (TPC) in Participants With Triple-Negative Breast Cancer (TNBC) Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response (pCR) at Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06393374
• Other study ID #: 2870-012
• Secondary ID: 2023-504962-52U1
• Status: Recruiting
• Phase: Phase 3
• Start date: June 21, 2024
• Est. completion date: December 14, 2037

Study information

• Verified date: June 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

This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (sac-TMT; MK-2870) in combination with pembrolizumab compared to treatment of physician's choice (TPC) in participants with triple-negative breast cancer (TNBC) who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery. The primary objective is to compare sac-TMT plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sac-TMT plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1530
• Est. completion date: December 14, 2037
• Est. primary completion date: December 16, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines

• Has no evidence of locoregional or distant relapse, as assessed by the treating physician

• Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to National Comprehensive Cancer Network (NCCN) treatment guidelines for TNBC

• Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery

• Has non-pathologic complete response at surgery

• Is able to continue on adjuvant pembrolizumab

• Randomization must be conducted within 12 weeks from surgical resection

• Completed adjuvant radiation therapy (if indicated) and recovered before randomization

• For male participants, agrees to refrain from donating sperm and either abstains from penile-vaginal intercourse or uses approved contraception for 100 days after the last dose of sac-TMT and 95 days after the last dose of capecitabine

• For female participants, is not a participant of childbearing potential (POCBP) or is a POCBP and uses highly effective contraception; agrees not to donate eggs for up to 190 days after the last dose of sac-TMT, 120 days after the last dose of pembrolizumab, and 185 days after the last dose of capecitabine; has a negative highly sensitive pregnancy test before the first dose of study intervention; and agrees to abstain from breastfeeding for at least 120 days after last dose of study therapy

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on Antiretroviral Therapy (ART)

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before first dose of study treatment

• 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 prior to randomization

Exclusion Criteria:

• Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) and is eligible for adjuvant therapy with olaparib where olaparib is approved and available

• Has Grade >2 peripheral neuropathy

• 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 including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to study intervention

• Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, Poly (ADP ribose) Polymerase (PARP) inhibitors, Antibody Drug Conjugates (ADCs), and/or immunotherapy, with the exception of adjuvant radiation therapy

• Is currently receiving a strong and/or moderate inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study

• Received prior radiotherapy within 3 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids

• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Cancer

Intervention

Biological:
• Pembrolizumab
Pembrolizumab 400 mg intravenous (IV) infusion q6w
• sac-TMT
sac-TMT 4 mg/kg IV infusion q2w

Drug:
• Capecitabine
Capecitabine 1000 mg/m^2 to 1250 mg/m^2 by mouth BID

Locations

Country	Name	City	State
United States	Virginia Cancer Institute ( Site 0034)	Richmond	Virginia
United States	Orchard Healthcare Research Inc. ( Site 0014)	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive Disease-Free Survival (iDFS)	iDFS is the time from randomization to invasive local, regional, or distant recurrence, invasive contralateral breast cancer, or death due to any cause, whichever occurs first.	Up to ~77 months
Secondary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to ~101 months
Secondary	Distant recurrence-free survival (DRFS)	DRFS is the time from randomization to distant recurrence or death due to any cause, whichever occurs first.	Up to ~101 months
Secondary	Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) Global Health Status/Quality of Life (QoL) Scores	EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life in cancer patients. The overall functioning score is based on participant responses that are scored on a 7-point scale (1 = "Very poor" to 7 = "Excellent"). Higher scores indicate better overall health status.	Baseline and up to ~60 months
Secondary	Change from baseline in EORTC QLQC30 Physical Functioning Score	EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. The physical functioning score is based on participant responses to questions that scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate better physical functioning.	Baseline and up to ~60 months
Secondary	Change from baseline in EORTC QLQC30 Role Functioning Score	EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. The physical functioning score is based on participant responses to questions that scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate better physical functioning.	Baseline and up to ~60 months
Secondary	Change from baseline in EORTC QLQC30 Fatigue Score	EORTC QLQ-C30 is a 30-item scale 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"). Lower scores indicate a better level of fatigue.	Baseline and up to ~60 months
Secondary	Number of participants with =1 adverse event (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 ~42 weeks
Secondary	Number of participants discontinuing from study therapy due to AE(s)	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 24 weeks

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary