Breast Neoplasms, Breast Cancer
Conditions
Brief summary
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.
Interventions
BIOLOGICALPatritumab deruxtecan
Administered via IV infusion as neoadjuvant treatment
BIOLOGICALPembrolizumab
Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2
DRUGPaclitaxel
Administered via IV infusion as neoadjuvant treatment
DRUGCarboplatin
Administered via IV infusion as neoadjuvant treatment
DRUGDoxorubicin hydrochloride
Administered 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
DRUGEpirubicin hydrochloride
Administered 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
DRUGCyclophosphamide
Administered 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
DRUGCapecitabine
Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2
DRUGOlaparib
Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2
Sponsors
Merck Sharp & Dohme LLC
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 is non-randomized. Part 2 is randomized 1:1:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * 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 an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 28 days prior to allocation/randomization * Has left ventricular ejection fraction (LVEF) of ≥50% or ≥ lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigate acquisition scan (MUGA) scan
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants Experiencing an Adverse Event (AE) | Up to ~43 weeks | 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) | Up to 21 days | 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 | Up to ~30 weeks | 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 | Up to ~30 weeks | 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: Number of Participants Experiencing an AE | Up to ~103 weeks | 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 2. |
| Part 2: Number of Participants who Discontinued Study Treatment Due to an AE | Up to ~90 weeks | 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 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: pCR-No Ductal Carcinoma in Situ (DCIS) Rate Using the Definition of ypT0 ypN0 | Up to ~30 weeks | 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) | Up to ~100 months | 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) | Up to ~100 months | 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) | Up to ~100 months | 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. |
| Part 2: Residual Cancer Burden (RCB) | Up to ~30 weeks | RCB is defined as residual disease in either the breast or lymph node at the time of surgery. RCB score provides a continuous measurement of the extent of residual cancer. There are four RCB classes: RCB-0 (RCB score 0), RCB-1 (0\< RCB score \<1.36), RCB-2 (1.36 \<RCB score \<3.28), and RCB-3 (RCB score \>3.28). |
Countries
South Korea, Spain, Taiwan, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed