Recruiting
Phase 2

Patritumab Deruxtecan & Pembrolizumab

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06797635

Conditions

Breast Neoplasms

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Patritumab deruxtecan

Pembrolizumab

Paclitaxel

Carboplatin

Doxorubicin hydrochloride

Study Details

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.

Conditions

Breast Neoplasms

Breast Cancer

Study ID

NCT06797635

Start date

Mar 20, 2025

Status verified date

May, 2026

Completion date

Dec 31, 2034

Anticipated

Primary completion date

Dec 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 exclusion criteria include but are not limited to the following:

  • 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
  • Has evidence of ongoing, uncontrolled, systemic bacterial, fungal, or viral infection
  • Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Has received any prior treatment, including radiation, systemic therapy, and/or definitive surgery for currently diagnosed breast cancer
  • Has received prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan)
  • Has metastatic (Stage IV) breast cancer or cN3 nodal involvement
  • Has known additional malignancy that is progressing or has required active treatment within the past 5 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current or suspected ILD
  • Has an active infection requiring systemic therapy
  • Has concurrent active HBV and HCV infection
  • Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness

Study Design

Enrollment

372 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin

In Part 1, participants receive neoadjuvant pembrolizumab 200 mg via intravenous (IV) infusion every 3 weeks (Q3W) plus patritumab deruxtecan via IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg via IV infusion Q3W plus paclitaxel 80 mg/m\^2 via IV infusion every week (QW) and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer.

experimental: Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion every Q3W plus patritumab deruxtecan (dose to be determined in part 1) IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks. At 3-6 weeks after last dose of neoadjuvant treatment, participants undergo surgery for breast cancer. After surgery, participants receive adjuvant pembrolizumab 400 mg IV every 6 weeks (Q6W) for \~30 weeks. Additional adjuvant treatment of physician's choice (TPC) may be given to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline BRCA mutation \[gBRCAm\] only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV Q3W or every 2 weeks (Q2W) and cyclophosphamide 600 mg/m\^2 IV Q3W or Q2W for 4 doses.

experimental: Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus patritumab deruxtecan (dose to be determined in part 1) via IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for \~30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W or Q2W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W or Q2W for 4 doses.

active comparator: Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for approximately 30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only) or capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles.

Interventions

Patritumab deruxtecan

Administered via IV infusion as neoadjuvant treatment

Pembrolizumab

Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2

Paclitaxel

Administered via IV infusion as neoadjuvant treatment

Carboplatin

Administered via IV infusion as neoadjuvant treatment

Doxorubicin 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

Epirubicin 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

Cyclophosphamide

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

Capecitabine

Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2

Olaparib

Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2

Primary outcome measure

  • Part 1: Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to ~43 weeks ]
  • Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to 21 days ]
  • Part 1: Number of Participants who Discontinued Study Treatment Due to an AE [ Time Frame: Up to ~30 weeks ]
  • Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 [ Time Frame: Up to ~30 weeks ]
  • Part 2: Number of Participants Experiencing an AE [ Time Frame: Up to ~103 weeks ]
  • Part 2: Number of Participants who Discontinued Study Treatment Due to an AE [ Time Frame: Up to ~90 weeks ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

UCLA Hematology/Oncology - Parkside ( Site 0021)

Recruiting

Santa Monica, California, United States, 90404

Contacts

Study Coordinator

424-402-9520

Orchard Healthcare Research Inc. ( Site 0006)

Recruiting

Skokie, Illinois, United States, 60077

Contacts

Study Coordinator

847-568-9932

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0003)

Recruiting

Billings, Montana, United States, 59102

Contacts

Study Coordinator

406-238-6685

Northwest Cancer Specialists (Compass Oncology) ( Site 8003)

Recruiting

Tigard, Oregon, United States, 97223

Contacts

Study Coordinator

360-944-9889

SCRI Oncology Partners ( Site 7000)

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Study Coordinator

844-482-4812

Texas Oncology - DFW ( Site 8000)

Recruiting

Dallas, Texas, United States, 75246

Contacts

Study Coordinator

214-370-1067

Houston Methodist Hospital ( Site 0022)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

713-441-9948

Virginia Oncology Associates (VOA) ( Site 8001)

Recruiting

Norfolk, Virginia, United States, 23502

Contacts

Study Coordinator

844-482-4812

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

May 20, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-05-20.