A clinical study of patritumab deruxtecan in people with breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Oct 2025 → ongoing

Decision date (initial)

2025-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Daiichi Sankyo Inc. · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-514376-40-00

WHO UTN

U1111-1307-7867

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Therapy, Pharmacokinetic, Efficacy, Safety, Pharmacogenetic, Others

1. Part 1 Objective: To evaluate safety and tolerability of neoadjuvant patritumab deruxtecan (HER3-DXd) plus pembrolizumab before carboplatin/ paclitaxel plus pembrolizumab.
2. Part 2 Objective: To compare HER3-DXd plus pembrolizumab before carboplatin/paclitaxel plus pembrolizumab versus carboplatin/paclitaxel plus pembrolizumab followed by AC/EC plus pembrolizumab with respect to rate of pCR (ypT0/Tis ypN0) at the time of definitive surgery, as assessed by local pathologist.
3. Part 2 Objective: To compare HER3-DXd plus pembrolizumab after carboplatin/paclitaxel plus pembrolizumab versus carboplatin/paclitaxel plus pembrolizumab followed by AC/EC plus pembrolizumab with respect to rate of pCR (ypT0/Tis ypN0) at the time of definitive surgery, as assessed by local pathologist.
4. Part 2: To evaluate safety and tolerability of study interventions in all arms.

Secondary objectives 5

1. Part 2: To evaluate the rate of pCR-no DCIS (ypT0 ypN0) at the time of definitive surgery in all arms, as assessed by local pathologist.
2. Part 2: To evaluate EFS in all arms, as assessed by the investigator.
3. Part 2: To evaluate OS in all arms.
4. Part 2: To evaluate DPDRFS in all arms, as assessed by the investigator.
5. Part 2: To evaluate RCB at the time of definitive surgery in all arms as assessed by local pathologist using the MD Anderson RCB calculator.

Conditions and MedDRA coding

High Risk Early-Stage Triple Negative Breast Cancer (TNBC) or Hormone Receptor Low Positive/Human Epidermal Growth Factor Receptor 2 Negative (HR-low+/HER2-) Breast Cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. 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
3. 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
4. Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 28 days prior to allocation/randomization
6. 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 13

1. Has uncontrolled or significant cardiovascular disease before randomization
2. Has clinically significant corneal disease
3. Has human immunodeficiency virus (HIV) infection with a history of Kaposi sarcoma and/or multicentric Castleman disease
4. 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
5. Has received any prior treatment, including radiation, systemic therapy, and/or definitive surgery for currently diagnosed breast cancer
6. 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)
7. Has metastatic (Stage IV) breast cancer or cN3 nodal involvement
8. Has known additional malignancy that is progressing or has required active treatment within the past 5 years
9. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
10. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, or where suspected ILD/pneumonitis cannot be ruled out by standard diagnostic assessments
11. Has an active infection requiring systemic therapy
12. Has concurrent active HBV and HCV infection
13. Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Part 1: Number of Participants Experiencing an Adverse Event (AE)
2. Part 1: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
3. Part 1: Number of Participants who Discontinued Study Treatment Due to an AE
4. Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0
5. Part 2: Number of Participants Experiencing an Adverse Event (AE)
6. Part 2: Number of Participants who Discontinued Study Treatment Due to an AE

Secondary endpoints 5

1. Part 2: Pathological Complete Response (pCR) Rate Using the Definition of ypT0 ypN0
2. Part 2: Event-Free Survival (EFS)
3. Part 2: Overall Survival (OS)
4. Part 2: Distant Progression or Distant Recurrence-Free Survival (DPDRFS)
5. Part 2: Residual Cancer Burden (RCB)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Alejandro Rios Hoyo

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Alejandro Rios Hoyo

Third parties 9

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications