Recruiting
Phase 3
Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012)
Condition(s) studied
Triple-Negative Breast Cancer
Investigational drug(s) / intervention(s)
PembrolizumabSacituzumab tirumotecanCapecitabine
Pembrolizumab: Pembrolizumab 400 mg intravenous (IV) infusion q6w
Sacituzumab tirumotecan: Sacituzumab tirumotecan 4 mg/kg IV infusion q2w
Capecitabine: Capecitabine 1000 mg/m\^2 to 1250 mg/m\^2 by mouth BID
Study summary
This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (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 sacituzumab tirumotecan plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sacituzumab tirumotecan plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.
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 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
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 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
Primary outcome measure(s)
- Invasive Disease-Free Survival (iDFS) — Up to ~77 months
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.
Trial sites (310)
| Facility | City | Region | Status |
| Infirmary Cancer Care ( Site 0001) |
Mobile |
Alabama |
Recruiting |
| Ironwood Cancer & Research Centers-Research ( Site 0054) |
Chandler |
Arizona |
Recruiting |
| MemorialCare Orange Coast Medical Center ( Site 9501) |
Fountain Valley |
California |
Recruiting |
| Scripps Cancer Center ( Site 0052) |
La Jolla |
California |
Recruiting |
| Cancer and Blood Specialty Clinic ( Site 0008) |
Los Alamitos |
California |
Completed |
| Kaiser Permanente - Oakland ( Site 0079) |
Oakland |
California |
Recruiting |
| Profound Research LLC ( Site 0105) |
Oceanside |
California |
Recruiting |
| Kaiser Permanente - Roseville ( Site 0081) |
Roseville |
California |
Recruiting |
| Kaiser Permanente - San Francisco ( Site 0080) |
San Francisco |
California |
Recruiting |
| Kaiser Permanente - Santa Clara ( Site 0082) |
Santa Clara |
California |
Recruiting |
| Providence Medical Foundation ( Site 9543) |
Santa Rosa |
California |
Recruiting |
| Kaiser Permanente Vallejo Medical Center ( Site 0060) |
Vallejo |
California |
Recruiting |
| Kaiser Permanente - Walnut Creek ( Site 0078) |
Walnut Creek |
California |
Recruiting |
| Bass Medical Group ( Site 0089) |
Walnut Creek |
California |
Completed |
| Cancer Centers of Colorado St. Mary's Regional Hospital ( Site 0046) |
Grand Junction |
Colorado |
Recruiting |
| University of Connecticut Health Center ( Site 0128) |
Farmington |
Connecticut |
Recruiting |
| Yale Cancer Center ( Site 0053) |
New Haven |
Connecticut |
Recruiting |
| Helen F. Graham Cancer Center & Research Institute ( Site 0018) |
Newark |
Delaware |
Recruiting |
| AdventHealth Altamonte Springs ( Site 0125) |
Altamonte Springs |
Florida |
Recruiting |
| Orlando Health Cancer Institute ( Site 0030) |
Orlando |
Florida |
Recruiting |
| Comprehensive Hematology Oncology ( Site 0091) |
St. Petersburg |
Florida |
Recruiting |
| Cleveland Clinic Martin North Hospital ( Site 0114) |
Stuart |
Florida |
Recruiting |
| Archbold Memorial Hospital-Lewis Hall Singletary Oncology Center ( Site 0040) |
Thomasville |
Georgia |
Completed |
| Illinois Cancer Specialists (ICS) ( Site 8010) |
Arlington Heights |
Illinois |
Recruiting |
| Orchard Healthcare Research Inc. ( Site 0014) |
Skokie |
Illinois |
Recruiting |
| Northwest Cancer Center - Dyer Clinic ( Site 0097) |
Dyer |
Indiana |
Recruiting |
| Parkview Research Center at Parkview Regional Medical Center ( Site 0011) |
Fort Wayne |
Indiana |
Recruiting |
| Cancer Center of Kansas ( Site 0004) |
Wichita |
Kansas |
Completed |
| Saint Elizabeth Medical Center Edgewood-Cancer Care Center ( Site 0044) |
Edgewood |
Kentucky |
Recruiting |
| CHRISTUS St. Frances Cabrini Hospital Center for Cancer Care ( Site 0109) |
Alexandria |
Louisiana |
Recruiting |
| Ochsner LSU Health - Monroe Medical Center, Family Medicine Clinic ( Site 0063) |
Monroe |
Louisiana |
Completed |
| Louisiana State University Health Sciences Shreveport ( Site 0029) |
Shreveport |
Louisiana |
Recruiting |
| Holy Cross Hospital ( Site 0069) |
Silver Spring |
Maryland |
Recruiting |
| University of Michigan ( Site 0103) |
Ann Arbor |
Michigan |
Recruiting |
| Henry Ford Health ( Site 0010) |
Detroit |
Michigan |
Recruiting |
| Profound Research LLC ( Site 0074) |
Royal Oak |
Michigan |
Completed |
| Metro-Minnesota Community Clinical Oncology ( Site 0031) |
Saint Louis Park |
Minnesota |
Recruiting |
| University of Mississippi Medical Center ( Site 0043) |
Jackson |
Mississippi |
Recruiting |
| SSM Health Cancer Care - Fenton ( Site 0088) |
Fenton |
Missouri |
Completed |
| Lake Regional Hospital ( Site 0009) |
Osage Beach |
Missouri |
Recruiting |
+ 270 more sites — see the full list on the official registry below.