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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
372
Administered via IV infusion as neoadjuvant treatment
Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2
Administered via IV infusion as neoadjuvant treatment
Administered via IV infusion as neoadjuvant treatment
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
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
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
Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2
Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2
UCLA Hematology/Oncology - Parkside ( Site 0021)
Santa Monica, California, United States
RECRUITINGOrchard Healthcare Research Inc. ( Site 0006)
Skokie, Illinois, United States
RECRUITINGIntermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003)
Billings, Montana, United States
RECRUITINGNorthwest Cancer Specialists (Compass Oncology) ( Site 8003)
Tigard, Oregon, United States
RECRUITINGSCRI Oncology Partners ( Site 7000)
Nashville, Tennessee, United States
RECRUITINGTexas Oncology - DFW ( Site 8000)
Dallas, Texas, United States
RECRUITINGHouston Methodist Hospital ( Site 0022)
Houston, Texas, United States
RECRUITINGVirginia Oncology Associates (VOA) ( Site 8001)
Norfolk, Virginia, United States
RECRUITINGSeoul National University Hospital ( Site 2400)
Seoul, South Korea
RECRUITINGSeverance Hospital, Yonsei University Health System ( Site 2402)
Seoul, South Korea
RECRUITING...and 7 more locations
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.
Time frame: Up to ~43 weeks
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.
Time frame: Up to 21 days
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.
Time frame: Up to ~30 weeks
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.
Time frame: Up to ~30 weeks
Part 2: Number of Participants Experiencing 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 experience an AE will be presented for Part 2.
Time frame: Up to ~103 weeks
Part 2: 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 2.
Time frame: Up to ~90 weeks
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.
Time frame: Up to ~30 weeks
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.
Time frame: Up to ~100 months
Part 2: Overall Survival (OS)
OS is defined as the time from randomization to date of death due to any cause.
Time frame: Up to ~100 months
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.
Time frame: Up to ~100 months
Part 2: Residual Cancer Burden (RCB)
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).
Time frame: Up to ~30 weeks
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