An Open-label Randomized Phase 2 Study to Evaluate Safety and Efficacy of Patritumab Deruxtecan Plus Pembrolizumab Administered Either Before or After Carboplatin/Paclitaxel Plus Pembrolizumab Compared With Pembrolizumab in Combination With Chemotherapy Followed by Surgery and Adjuvant Pembrolizumab for High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer (HERTHENA-Breast03)
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.
Arms & 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
Outcome measures
Primary
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
Secondary
Part 2: pCR-No Ductal Carcinoma in Situ (DCIS) Rate Using the Definition of ypT0 ypN0
Time frame: Up to ~30 weeks
Part 2: Event-Free Survival (EFS)
Time frame: Up to ~100 months
Part 2: Overall Survival (OS)
Time frame: Up to ~100 months
Part 2: Distant Progression or Distant Recurrence-Free Survival (DPDRFS)
Time frame: Up to ~100 months
Part 2: Residual Cancer Burden (RCB)
Time frame: Up to ~30 weeks
Eligibility criteria
Study locations (8)
UCLA Hematology/Oncology - Parkside ( Site 0021)
Santa Monica, California, 90404
Orchard Healthcare Research Inc. ( Site 0006)
Skokie, Illinois, 60077
Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003)
Billings, Montana, 59102
Northwest Cancer Specialists (Compass Oncology) ( Site 8003)
Tigard, Oregon, 97223
SCRI Oncology Partners ( Site 7000)
Nashville, Tennessee, 37203
Texas Oncology - DFW ( Site 8000)
Dallas, Texas, 75246
Houston Methodist Hospital ( Site 0022)
Houston, Texas, 77030
Virginia Oncology Associates (VOA) ( Site 8001)
Norfolk, Virginia, 23502