U3-1402 for Metastatic Breast Cancer

No longer recruiting at 13 trial locations

Overseen By Sarah Cannon Development Innovations, LLC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SCRI Development Innovations, LLC

Must be taking: Endocrine therapy, CDK 4/6 inhibitor

Must not be taking: Chloroquine, Hydroxychloroquine

Disqualifiers: ILD, Severe pulmonary, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 33 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, U3-1402 (patritumab deruxtecan), for individuals with advanced breast cancer that has spread to other parts of the body. The primary goal is to determine if this treatment is safe and effective for various types of metastatic breast cancer, including hormone-receptor positive, HER2-negative, and triple-negative types. Participants should have previously tried certain cancer treatments without success. This trial may suit individuals with advanced breast cancer who have undergone frequent treatments and seek new options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer treatments, including chemotherapy, biologic, hormonal agents, or immune checkpoint inhibitors, at least 21 days before starting the study drug. Additionally, chloroquine or hydroxychloroquine must be stopped 14 days prior to the first dose. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that U3-1402, also known as patritumab deruxtecan, is generally safe. While some side effects occur, most people find them manageable. Studies have found that this treatment can benefit patients who have already tried other therapies.

One study noted that some patients developed a lung condition called interstitial lung disease (ILD). In these cases, symptoms usually improved quickly, often within a month. Overall, patritumab deruxtecan appears well-tolerated, even by patients who have undergone many previous treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for metastatic breast cancer?

Unlike the standard treatments for metastatic breast cancer, which often include hormone therapies or chemotherapy, U3-1402 (Patritumab Deruxtecan) is unique because it targets the HER3 receptor, a novel approach in this setting. This treatment combines an antibody with a cancer-killing drug, which allows it to deliver chemotherapy directly to cancer cells that express HER3, potentially increasing the treatment's effectiveness while minimizing damage to healthy cells. Researchers are excited about U3-1402's ability to address different types of metastatic breast cancer, including hormone-receptor-positive, triple-negative, and HER2-positive subtypes, providing a versatile option that could enhance outcomes across a broad range of patients.

What evidence suggests that U3-1402 might be an effective treatment for metastatic breast cancer?

Research has shown that U3-1402, also known as patritumab deruxtecan, may help treat advanced breast cancer. Studies have found it effective for patients who have already tried several other treatments. This drug combines targeted therapy and chemotherapy to kill cancer cells more effectively. Participants in this trial will receive U3-1402. Earlier studies demonstrated that patients responded well, experiencing manageable side effects and long-lasting benefits across different types of breast cancer. This suggests that U3-1402 could be a helpful option for those with advanced breast cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Erika Hamilton, MD

Principal Investigator

SCRI Development Innovations, LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic breast cancer who have tried certain treatments without success. Eligible patients must not be pregnant, should agree to use two forms of contraception, and cannot have severe heart conditions or active infections like hepatitis or HIV. They also need to have at least one measurable tumor lesion and acceptable organ function.

Inclusion Criteria

You must have at least one measurable tumor according to specific guidelines, except if the cancer has only spread to the bones.

I am using two forms of birth control, including a barrier method, and will continue for 7 months after the last dose.

I had brain metastases treatment over 4 weeks ago, no worsening, mild symptoms, and don't need steroids.

Exclusion Criteria

I don't have any severe side effects from past treatments, except for hair loss.

I do not have active brain or spinal cord complications needing steroids or seizure meds.

I haven't taken chloroquine or hydroxychloroquine in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 every 3 weeks

Up to 33 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 days

Extension

Participants may continue to be monitored for disease progression or death

Up to 33 months

What Are the Treatments Tested in This Trial?

Interventions

• U3-1402

Trial Overview The study tests U3-1402 (patritumab deruxtecan), an antibody drug conjugate, for safety and effectiveness in treating locally advanced or metastatic breast cancer. Participants will receive this experimental medication to see if it helps control their cancer better than current treatments.

How Is the Trial Designed?

Group I: Part Z Experimental Treatment 1 Intervention

Participants will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 every 3 weeks. Part Z will enroll an additional 21 participants with HER2+ MBC.

Group II: Part B Experimental Treatment 1 Intervention

Participants will receive 5.6 mg/kg U3-1402 intravenously on day 1 every 3 weeks. Part B will enroll 20 participants with metastatic hormone-receptor positive (HR+) HER2-negative cancer and 20 participants with metastatic triple-negative breast cancer (mTNBC), regardless of HER3 expression.

Group III: Part A Experimental Treatment 1 Intervention

Participants will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 every 3 weeks. All participants will undergo pre-treatment biopsies. (An archival tissue sample taken within two months of treatment should be provided if it is not medically feasible to provide a pre-treatment biopsy). Up to 60 participants will be enrolled into this arm.

Who Is Running the Clinical Trial?

SCRI Development Innovations, LLC

Lead Sponsor

Trials

193

Recruited

13,800+

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Industry Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Published Research Related to This Trial

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, was analyzed using pharmacokinetics data from 425 patients with solid tumors, showing a well-defined clearance and distribution profile that supports its use in clinical settings.

The study found that factors like weight, albumin levels, sex, and tumor type had mild effects on drug exposure, indicating that no significant dose adjustments are needed for different patient subpopulations in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Patritumab Deruxtecan in Patients With Solid Tumors. Lu, Y., Shimizu, S., Sawamura, R., et al.[2023]

The study is investigating the HER3-directed antibody drug conjugate patritumab deruxtecan (HER3-DXd) in patients with HR-positive/HER2-negative early breast cancer, focusing on its biological effects after a single dose.

The primary endpoint is to assess the CelTIL score, which will help evaluate the drug's impact on the tumor microenvironment and resistance mechanisms, providing valuable insights into its efficacy and potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer. Pascual, T., Oliveira, M., Ciruelos, E., et al.[2021]

Patritumab deruxtecan (HER3-DXd) showed promising efficacy in treating advanced breast cancer, with objective response rates of 30.1% in hormone receptor-positive/HER2-negative patients and 42.9% in HER2-positive patients, indicating its potential as a treatment option for various breast cancer subtypes.

The safety profile of HER3-DXd was manageable, with common treatment-emergent adverse events including gastrointestinal and hematologic toxicities; however, 71.4% of patients experienced grade ≥3 adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. Krop, IE., Masuda, N., Mukohara, T., et al.[2023]

In a study of 77 patients with early breast cancer, a single dose of patritumab deruxtecan (HER3-DXd) significantly increased the CelTIL score, indicating enhanced immune infiltration and a shift towards a less proliferative tumor phenotype.

The treatment showed a clinical response rate of 45% among patients, with most experiencing manageable side effects, suggesting HER3-DXd has a tolerable safety profile and warrants further investigation in early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study. Oliveira, M., Falato, C., Cejalvo, JM., et al.[2023]

In a phase II study involving 225 patients with advanced EGFR-mutated non-small-cell lung cancer, HER3-DXd demonstrated a confirmed objective response rate of 29.8%, indicating meaningful efficacy after prior treatments with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy.

The safety profile of HER3-DXd was manageable and tolerable, with median overall survival of 11.9 months and notable efficacy in patients with nonirradiated brain metastases, showing a CNS objective response rate of 33.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. Yu, HA., Goto, Y., Hayashi, H., et al.[2023]

Citations

1. nature.com nature.com/articles/s41591-025-03885-3

Patritumab deruxtecan in HR+HER2− advanced breast ... Trastuzumab deruxtecan (T-DXd) has substantiallyimproved survival outcomes in patients with HER2 (also known as ERBB2)-expressing breast cancer ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37801674/

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal ... Conclusion: HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.1004

A phase 2 study of HER3-DXd in patients (pts) with ... This 3-part Phase 2 study examines efficacy of HER3-DXd across MBC subsets and defines the pt population likely to derive greater benefit.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04699630

A Study of U3-1402 (Patritumab Deruxtecan) in Subjects ... This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 (patritumab deruxtecan) in patients with locally advanced or metastatic ...

5. daiichisankyo.us daiichisankyo.us/press-releases/-/article/herthena-breast04-phase-3-trial-of-patritumab-deruxtecan-initiated-in-patients-with-metastatic-hormone-receptor-positive-her2-negative-breast-cancer-previously-treated-with-endocrine-therapy

HERTHENA-Breast04 Phase 3 Trial of Patritumab ... HERTHENA-Breast04 is an open-label, randomized, phase 3 trial evaluating the safety and efficacy of patritumab deruxtecan (5.6 mg/kg) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04699630

A Study of U3-1402 (Patritumab Deruxtecan) in Subjects ... This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 (patritumab deruxtecan) in patients with locally advanced or metastatic ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00882

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal ... HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data ...