U3-1402 for Metastatic Breast Cancer

Recruiting at 11 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

121 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 (patritumab deruxtecan) in patients with locally advanced or metastatic breast cancer (MBC).

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.

What data supports the effectiveness of the drug U3-1402 (Patritumab deruxtecan) for treating metastatic breast cancer?

Research shows that Patritumab deruxtecan, a drug targeting a protein called HER3, has shown promise in treating breast cancer that expresses this protein. It has been tested in patients with advanced breast cancer and has shown biological activity, suggesting it could be effective in this condition. ^{1 2 3 4 5}

Is Patritumab Deruxtecan safe for humans?

Patritumab Deruxtecan has been tested in various clinical trials for different cancers, including breast and lung cancer. These studies generally focus on its safety and effectiveness, and while specific side effects are not detailed here, the trials suggest it is being carefully evaluated for safety in humans. ^{1 2 3 4 5}

What makes the drug U3-1402 unique for treating metastatic breast cancer?

U3-1402, also known as Patritumab deruxtecan, is unique because it targets the HER3 protein, which is often found in high levels in breast cancer cells, and delivers a cancer-killing drug directly to these cells. This targeted approach may offer a new option for patients with HER3-expressing metastatic breast cancer, where standard treatments may not be effective. ^{1 2 3 4 5}

Research Team

Erika Hamilton, MD

Principal Investigator

SCRI Development Innovations, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. Switzerland 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. [2021]

3. United States 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. [2023]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Patritumab Deruxtecan in Patients With Solid Tumors. [2023]