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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06393374




Registration number
NCT06393374
Ethics application status
Date submitted
26/04/2024
Date registered
1/05/2024
Date last updated
21/11/2024

Titles & IDs
Public title
Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012)
Scientific 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
Secondary ID [1] 0 0
2023-504962-52
Secondary ID [2] 0 0
2870-012
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple-Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - sac-TMT
Treatment: Drugs - Capecitabine

Experimental: Pembrolizumab + sac-TMT - Participants receive pembrolizumab every 6 weeks (q6w) in combination with sac-TMT every 2 weeks (q2w) for 24 weeks. In addition, participants receive an antihistamine, an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to sac-TMT infusions.

Active comparator: Treatment of Physician's Choice - Participants receive pembrolizumab q6w or pembrolizumab q6w in combination with capecitabine (twice daily \[BID\] on Days 1 to 14 and 22 to 35 every 42 days x 4 \[2 weeks 1, 1 week off\]) for 24 weeks.


Treatment: Other: Pembrolizumab
Pembrolizumab 400 mg intravenous (IV) infusion q6w

Treatment: Other: sac-TMT
sac-TMT 4 mg/kg IV infusion q2w

Treatment: Drugs: Capecitabine
Capecitabine 1000 mg/m\^2 to 1250 mg/m\^2 by mouth BID
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Invasive Disease-Free Survival (iDFS)
Timepoint [1] 0 0
Up to ~77 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to ~101 months
Secondary outcome [2] 0 0
Distant recurrence-free survival (DRFS)
Timepoint [2] 0 0
Up to ~101 months
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline and up to ~60 months
Secondary outcome [4] 0 0
Change from baseline in EORTC QLQC30 Physical Functioning Score
Timepoint [4] 0 0
Baseline and up to ~60 months
Secondary outcome [5] 0 0
Change from baseline in EORTC QLQC30 Role Functioning Score
Timepoint [5] 0 0
Baseline and up to ~60 months
Secondary outcome [6] 0 0
Change from baseline in EORTC QLQC30 Fatigue Score
Timepoint [6] 0 0
Baseline and up to ~60 months
Secondary outcome [7] 0 0
Number of participants with =1 adverse event (AE)
Timepoint [7] 0 0
Up to ~42 weeks
Secondary outcome [8] 0 0
Number of participants discontinuing from study therapy due to AE(s)
Timepoint [8] 0 0
Up to 24 weeks

Eligibility
Key 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
* Has provided tissue from the surgical resection for central laboratory determination of trophoblast cell surface antigen 2 (TROP2) status
* If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (100 days for MK-2870 and 95 days for capecitabine [no restriction for pembrolizumab]) AND agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
* For females (assigned at birth), is not pregnant or breastfeeding and =1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraction after the last dose of study intervention (190 days for MK-2870, 120 days for pembrolizumab, and 185 days for capecitabine). Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention
* Participants who have AEs due to previous anticancer therapies must have recovered to =Grade 1 or baseline (except alopecia)
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) or a topoisomerase I inhibitor-containing ADC
* Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, Poly (ADP ribose) Polymerase (PARP) inhibitors, ADCs, and/or immunotherapy, with the exception of adjuvant radiation therapy
* Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period before starting MK-2870 is 2 weeks
* Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
* Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization
* Received prior radiotherapy within 3 weeks of start of study intervention or required corticosteroids for radiation related toxicities that cannot be discontinued before the first dose of study intervention
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has known additional malignancy that is progressing or has required active treatment within the past 5 years
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has concurrent active hepatitis B and hepatitis C virus infection
* Has history of allogeneic tissue/solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/12/2037
Actual
Sample size
Target
1530
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Macquarie University-MQ Health Clinical Trials Unit ( Site 2703) - Macquarie University
Recruitment hospital [2] 0 0
Westmead Hospital-Westmead Breast Cancer Institute ( Site 2700) - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si - Brisbane
Recruitment hospital [4] 0 0
Frankston Hospital-Oncology and Haematology ( Site 2704) - Frankston
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Caba
Country [15] 0 0
Argentina
State/province [15] 0 0
Santa Fe
Country [16] 0 0
Austria
State/province [16] 0 0
Salzburg
Country [17] 0 0
Belgium
State/province [17] 0 0
Bruxelles-Capitale, Region De
Country [18] 0 0
Belgium
State/province [18] 0 0
Oost-Vlaanderen
Country [19] 0 0
Belgium
State/province [19] 0 0
Namur
Country [20] 0 0
Brazil
State/province [20] 0 0
Ceara
Country [21] 0 0
Brazil
State/province [21] 0 0
Piaui
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio Grande Do Sul
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Czechia
State/province [25] 0 0
Brno-mesto
Country [26] 0 0
Czechia
State/province [26] 0 0
Jihocesky Kraj
Country [27] 0 0
Czechia
State/province [27] 0 0
Olomoucky Kraj
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha 2
Country [29] 0 0
Czechia
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Praha 5
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Finland
State/province [30] 0 0
Pirkanmaa
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Finland
State/province [31] 0 0
Uusimaa
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Finland
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Varsinais-Suomi
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France
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Aquitaine
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France
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Nord
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France
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Rhone-Alpes
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Germany
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Baden-Wurttemberg
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Germany
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Nordrhein-Westfalen
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Germany
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Saarland
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Germany
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Berlin
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Greece
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Attiki
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Greece
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Kentriki Makedonia
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Greece
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Thessalia
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Greece
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Thessaloniki
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Hong Kong
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Hong Kong
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Ireland
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Cork
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Ireland
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Dublin
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Israel
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Jerusalem
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Israel
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Petah Tikva
Country [49] 0 0
Israel
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Ramat Gan
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Italy
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Campania
Country [51] 0 0
Italy
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Catania
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Italy
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Friuli-Venezia Giulia
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Toscana
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Italy
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Bologna
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Italy
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Novara
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Korea, Republic of
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Seoul
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Malaysia
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Kuala Lumpur
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Norway
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Buskerud
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Norway
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Rogaland
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Norway
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Oslo
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Poland
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Kujawsko-pomorskie
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Poland
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Mazowieckie
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Poland
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Podlaskie
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Pomorskie
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Poland
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Slaskie
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Poland
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Zachodniopomorskie
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Portugal
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Lisboa
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Portugal
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Porto
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Spain
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Andalucia
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Spain
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Barcelona
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Spain
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La Coruna
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Spain
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Madrid, Comunidad De
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Spain
State/province [75] 0 0
Valenciana, Comunitat
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Spain
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Madrid
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Spain
State/province [77] 0 0
Valencia
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Switzerland
State/province [78] 0 0
Berne
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Switzerland
State/province [79] 0 0
Geneve
Country [80] 0 0
Switzerland
State/province [80] 0 0
Grisons
Country [81] 0 0
Switzerland
State/province [81] 0 0
Zurich
Country [82] 0 0
Switzerland
State/province [82] 0 0
Fribourg
Country [83] 0 0
United Kingdom
State/province [83] 0 0
England
Country [84] 0 0
United Kingdom
State/province [84] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT06393374
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06393374