Researchers are looking for new ways to treat triple-negative breast cancer (TNBC) and hormone receptor (HR) low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. The main goals of this study are to learn:
* About the safety of the study treatments and if people tolerate them * If people who receive patritumab deruxtecan, pembrolizumab, and chemotherapy before surgery have fewer cancer cells removed during surgery compared to those who receive only pembrolizumab (pembro) and chemotherapy.
Has locally advanced, non-metastatic (M0), breast cancer, defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee on Cancer (AJCC) criteria: cT1c, N1-N2; cT2, N0-N2; cT3, N0-N2; or cT4a-d, N0-N2
Has centrally confirmed diagnosis of breast cancer that is triple-negative or HR-low+/HER2- breast cancer that will be treated according to the triple-negative breast cancer (TNBC) paradigm
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
Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Has uncontrolled or significant cardiovascular disease before randomization
Has any history of or evidence of any current leptomeningeal carcinomatosis.
Has clinically significant corneal disease
Has human immunodeficiency virus (HIV) infection with a history of Kaposi sarcoma and/or multicentric Castleman disease
Parallel
Patritumab deruxtecan
Biological/VaccineAdministered via IV infusion as neoadjuvant treatment
Pembrolizumab
Biological/VaccineAdministered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2
Paclitaxel
DrugAdministered via IV infusion as neoadjuvant treatment
Carboplatin
DrugAdministered via IV infusion as neoadjuvant treatment
Doxorubicin hydrochloride
DrugAdministered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2
Epirubicin hydrochloride
DrugAdministered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2
Cyclophosphamide
DrugAdministered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2
Capecitabine
DrugAdministered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2
Olaparib
DrugAdministered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2
Part 1: Number of Participants Experiencing an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented for Part 1.
Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
A DLT is defined by the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, assessed by investigator as drug-related: Grade (gr) 3 or 4 nonhematologic toxicity (with exceptions); gr 3 or gr 4 laboratory values (with exceptions); gr 3 or 4 febrile neutropenia; prolonged delay (\>2 weeks) in initiating Cycle 2 (cycle length = 3 weeks) due to intervention-related toxicity; any intervention-related toxicity that causes the participant to discontinue intervention during Cycle 1; interstitial lung disease as per investigator; any other gr ≥3 pulmonary toxicity; or gr 5 toxicity.
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinued study treatment due to an AE will be presented for Part 1.
Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy at the time of definitive surgery.
Part 2: pCR-No Ductal Carcinoma in Situ (DCIS) Rate Using the Definition of ypT0 ypN0
pCR-no DCIS (ypT0 ypN0) is defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy at the time of definitive surgery.
Part 2: Event-Free Survival (EFS)
EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first.
Part 2: Overall Survival (OS)
OS is defined as the time from randomization to date of death due to any cause.
Part 2: Distant Progression or Distant Recurrence-Free Survival (DPDRFS)
DPDRFS is defined as the time from randomization to first distant progression or distant recurrence event as assessed or death due to any cause, whichever occurs first.
Click on the lead sponsor to view all of their trials.
Merck Sharp & Dohme LLC
Lead sponsor
Daiichi Sankyo
Collaborator
