C50 Cancer de mama
Conditions
Interventions
sac-TMT (MK-2870): Powder lyophilized for solution dose strength 200 mg/vial. Dosage levels of 4 mg/kg by IV infusion the first day of every 2 weeks. Participants are required to be premedicated start
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Type of Participant and Disease Characteristics: 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. Has provided an acceptable new, recently obtained, or archival core or excisional biopsy of a tumor lesion not previously irradiated for central confirmation of TNBC, PD-L1 and TROP2 expression. Tissue preference is described in Section 8.1.13. Note: If the central laboratory indicates that a specimen is inadequate for testing, an additional sample may be requested. Has central laboratory confirmed TNBC that is evaluable for PD-L1 and TROP2: a. TNBC is defined as ER<1%, PgR<1%, and HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH negative). Note: Participants previously diagnosed with early-stage HER2-positive or HR-positive/HER2-negative breast cancer are allowed if the most recent tumor specimen from a locally recurrent or distant metastatic lesion shows centrally confirmed TNBC. b. Results of centrally determined TROP2 and PD-L1 must be known for eligibility and stratification. Participants with no detectable TROP2 expression will be classified in the TROP2 “low” stratum. Participants with de novo metastatic TNBC are eligible if in the opinion of the treating investigator the proposed study intervention is in the best interest of the participant. Participants previously treated with systemic therapy for early-stage breast cancer must have received an anthracycline and/or taxane in the (neo)adjuvant setting (unless contraindicated). Participants originally diagnosed with early-stage breast cancer who did not receive any treatment and subsequently developed metastatic disease are eligible. Assigned Female Sex at Birth: A participant assigned female sex at birth is eligible to participate if not breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention. 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, with the exception of endocrine therapy (for participants whose initial disease was HR-positive) and adjuvant bisphosphonate (if administered). Prior ICI is acceptable. Note 1: The date of completion of therapy for early-stage breast cancer with curative intent is defined as: end of the neoadjuvant therapy, date of first breast surgery, or end of the adjuvant therapy, whichever is later. Note 2: First documentation of local or distant disease recurrence must be in the form of a dated biopsy, pathology, or imaging study report. Is a candidate for treatment with one of the TPC options: paclitaxel or nab-paclitaxel or gemcitabine + carboplatin. Note: Participants who received taxane and/or platinum agents in the adjuvant/neoadjuvant setting can be treated with same class(es) of chemotherapy (taxane or gemcitabine/carboplatin), if =6 months have elapsed between the completion of taxane and/or platinum agents with curative intent (ie, date of last adjuvant/neoadjuvant chemotherapy administration [whichever occurred last] and date of first documented local or distant disease recurrence). Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. Note
Exclusion criteria
Exclusion criteria: Active infection requiring systemic therapy other than those permitted in Section 5.1. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Has known deleterious or suspected deleterious germline BRCA mutation, receiving care where PARP inhibitors are approved and available. Note: Testing for germline BRCA mutations is not required and should be performed as clinically indicated. Medical Conditions: Has breast cancer amenable to treatment with curative intent. Has TNBC with evaluable tumor PD-L1 expression at CPS=10 as determined by central laboratory using PD-L1 22C3 IHC pharmDx. Has received prior systemic therapy for treatment of locally recurrent unresectable or metastatic TNBC. Participants with PD-L1 expression on tumor-infiltrating immune cells as a percentage of tumor area =1% by the SP142 assay who are candidates for treatment with atezolizumab per local standard of care (where approved and available) are considered ineligible. Note: PD-L1 testing by SP142 is not required. Refer to Appendix 7 for country-specific requirements. 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 (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 the 6 months preceding study intervention. Has skin only metastatic disease. Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, bone marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, shortness of breath requiring supplemental oxygen, symptomatic pleural effusion requiring supplemental oxygen, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or the need to achieve rapid symptom control. Note: - Participants with symptomatic pleural effusion who have dyspnea at rest requiring supplemental oxygen, but which is alleviated by drainage of the fluid can be enrolled. - Participants with symptomatic ascitic effusion caused by peritoneal carcinomatosis, which is alleviated after drainage of the ascitic fluid can be enrolled. - Participants with symptomatic liver metastases include participants with rapidly increasing bilirubin >1.5 x ULN in the absence of biliary obstruction with involvement of over than 50% of liver parenchyma by the disease. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. Prior/Concomitant Therapy: Received prior treatment with a TROP2-targeted ADC. Received prior treatment with an ADC with a topoisomerase 1 inhibitor payload. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period before starting sac-TMT is 2 weeks. Note: A list of strong inhibitors or inducers of CYP3A4 can be f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Elapsed time measurement. Testing: Stratified Log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free Survival (PFS) - for treatment comparison of sac-TMT to TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.;Elapsed time measurement. Testing: Stratified Log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free Survival (PFS) - for treatment comparison of sac-TMT plus pembrolizumab to TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.;Elapsed time measurement. Testing: Stratified Log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Overall Survival (OS) for treatment comparison of sac-TMT to TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR. Testing and estimation: Stratified Miettinen and Nurminen method. NAME OF THE RESULT: Objective Response (OR) - for treatment comparison of sac-TMT plus pembrolizumab to TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study;Elapsed time measurement. NAME OF THE RESULT: Duration of Overall Response (DOR) to evaluate sac-TMT, sac-TMT plus pembrolizumab, and TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.;Elapsed time measurement. NAME OF THE RESULT: Duration of Overall Response (DOR) to evaluate sac-TMT, sac-TMT plus pembrolizumab, and TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.;Change from baseline in EORTC QLQ-C30 global health status/quality of life score, physical functioning, emotional functioning, fatigue and diarrhea. NAME OF THE RESULT: Mean change from baseline in HRQoL using the EORTC QLQ-C30 PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study.;Clinical review of all relevant parameters including adverse events, laboratory values, and vital signs. NAME OF THE RESULT: Safety and tolerability of sac-TMT, sac-TMT plus pembrolizumab, and TPC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study.;Elapsed time measurement. Testing: Stratified Log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Overall Survival (OS) for treatment comparison of sac-TMT to TPC | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea South, Malasya, Mexico, Nederland, New Zealand, Peru, Philippines, Poland, Romania, Spain, Taiwan, Thailand, Turkey, United Kindgdom, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed