Resumen

Este es un estudio aleatorizado y abierto que compara la eficacia y la seguridad de sacituzumab tirumotecan (MK-2870) adyuvante en combinación con pembrolizumab frente al tratamiento a elección del médico (TEM) en participantes con cáncer de mama triple negativo (CMTN) que recibieron terapia neoadyuvante y no alcanzaron respuesta patológica completa (RPC) en la cirugía. El objetivo primario es comparar sacituzumab tirumotecan más pembrolizumab frente al TEM (pembrolizumab o pembrolizumab más capecitabina) con respecto a la supervivencia libre de enfermedad invasiva (SLEI) según la evaluación del investigador. Se plantea la hipótesis de que sacituzumab tirumotecan más pembrolizumab es superior al TEM con respecto a la SLEI según la evaluación del investigador.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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 16 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 (120 days for sacituzumab tirumotecan and 95 days for capecitabine \[no restriction for pembrolizumab\]): 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 contraception after the last dose of study intervention (210 days for sacituzumab tirumotecan, 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 birus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization

Criterios de exclusión

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 severe corneal disease that prevents/delays corneal healing
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
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 (adenosine diphosphate 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 sacituzumab tirumotecan 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, cytotoxic T-lymphocyte-associated protein-4 \[CTLA-4\], OX-40 \[cluster of differentiation (CD) 134\], or 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

Ubicaciones

Hospital Aleman-Oncology ( Site 0501)

Capital Federal, Buenos Aires, Argentina

Study Coordinator · +541148277000

RECRUITING

Hospital Británico de Buenos Aires-Oncology ( Site 0502)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · +54911563819972

RECRUITING

Instituto de Oncología Angel H. Roffo ( Site 0503)

Buenos Aires, Buenos Aires F.D., Argentina

Study Coordinator · 5491152375236

RECRUITING

Instituto Alexander Fleming-Alexander Fleming ( Site 0509)

Buenos Aires, Buenos Aires F.D., Argentina

Study Coordinator · +5491138850425

RECRUITING

Sanatorio Parque ( Site 0512)

Rosario, Santa Fe Province, Argentina

Study Coordinator · 543414929663

RECRUITING

Sanatorio Finochietto ( Site 0513)

Buenos Aires, Argentina

Study Coordinator · +54 113752-8000

RECRUITING

Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 0508)

Buenos Aires, Argentina

Study Coordinator · +541152991580

RECRUITING

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Sacituzumab tirumotecan

Capecitabine

Ubicaciones

Hospital Aleman-Oncology ( Site 0501)

Hospital Británico de Buenos Aires-Oncology ( Site 0502)

Instituto de Oncología Angel H. Roffo ( Site 0503)

Instituto Alexander Fleming-Alexander Fleming ( Site 0509)

Sanatorio Parque ( Site 0512)

Sanatorio Finochietto ( Site 0513)

Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 0508)

Patrocinadores

Contactos

Toll Free Number