Disitamab Vedotin + Tucatinib for Breast Cancer

Recruiting at 131 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Seagen Inc.

Must not be taking: ADCs, Tucatinib

Disqualifiers: Active CNS metastasis, Other malignancy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer. Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2. This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®. This study will test how safe and how well DV with tucatinib works for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received any systemic anticancer treatment within 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug Disitamab Vedotin + Tucatinib for breast cancer?

Disitamab Vedotin has shown strong anti-tumor activity in breast cancer models with HER2-positive and low HER2 expression, and has been effective in treating other cancers like gastric cancer. It has also been used successfully in patients with advanced breast cancer, including those with brain metastases, achieving long-term remission in some cases. ^{1 2 3 4 5}

Is the combination of Disitamab Vedotin and Tucatinib safe for humans?

Disitamab Vedotin has been shown to have a wider therapeutic window and less toxicity to normal tissues compared to other HER2-targeting agents, indicating it may be safer for human use. Tucatinib is described as a well-tolerated treatment option for patients with advanced HER2-positive breast cancer, suggesting it is generally safe for humans. ^{1 2 3 5 6}

What makes the drug Disitamab Vedotin unique for breast cancer treatment?

Disitamab Vedotin is unique because it is an antibody-drug conjugate that targets HER2, a protein often overexpressed in breast cancer, and delivers a potent chemotherapy agent directly to cancer cells, potentially reducing harm to normal tissues. It has shown promise in treating HER2-positive and low HER2-expressing breast cancers, even in cases with brain metastases, where other treatments may not be as effective. ^{1 2 3 4 5}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with advanced breast or gastric cancer that has HER2 proteins, which can make the cancer grow faster. Participants must have a certain level of health and fitness (ECOG score 0-1) and measurable disease according to specific criteria. They should have tried standard treatments without success or be unable to tolerate them.

Inclusion Criteria

My cancer is advanced and cannot be removed by surgery.

I have had 3 or fewer chemotherapy treatments for my advanced breast cancer.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib

I have been treated with tucatinib before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluation of disitamab vedotin plus tucatinib to determine safe and effective dose levels

Duration not specified

Dose Optimization

Assessment of identified dose levels for safety and efficacy in HER2-low LA/mBC subjects

Duration not specified

Expansion

Evaluation of disitamab vedotin plus tucatinib in expansion cohorts for HER2 low mGC/GEJC and HER2+ LA/mBC

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 years

Treatment Details

Interventions

• Disitamab Vedotin (Antibody Drug Conjugate)
• Tucatinib (Small Molecule Inhibitor)

Trial Overview The study is testing disitamab vedotin (DV), an experimental drug designed to target and kill cancer cells, alone or combined with tucatinib, a drug approved in the US for treating cancer. The goal is to see how safe these drugs are for patients with solid tumors expressing HER2 and what side effects they may cause.

Participant Groups

Group I: Dose Optimization - HER2-low and HER2+ LA/mGC/GEJC Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Group II: Dose Optimization - HER2-low and HER2+ LA/mBC Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Group III: Dose Expansion - HER2-low LA/mGC/GEJC Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Group IV: Dose Expansion - HER2-low LA/mBC Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Group V: Dose Expansion - HER2+ LA/mGC/GEJC Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Group VI: Dose Expansion - HER2+ LA/mBC Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Group VII: Dose Escalation - Previously treated advanced GC/GEJC or breast cancer Experimental Treatment 2 Interventions

disitamab vedotin + tucatinib

Who Is Running the Clinical Trial?

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

RemeGen Co., Ltd.

Industry Sponsor

Trials

84

Recruited

11,100+

Dr. Jianmin Fang

RemeGen Co., Ltd.

Chief Executive Officer since 2008

PhD in Molecular Biology

Dr. Ruyi He

RemeGen Co., Ltd.

Chief Medical Officer since 2023

MD

Findings from Research

Disitamab vedotin, an antibody-drug conjugate targeting HER2, received its first approval in China for treating HER2-overexpressing locally advanced or metastatic gastric cancer after patients have undergone at least two chemotherapy regimens.

The drug is also being explored for use in other solid tumors, including urothelial cancer and various types of breast cancer, indicating its potential as a versatile treatment option in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disitamab Vedotin: First Approval. Deeks, ED.[2023]

Disitamab vedotin (RC48) is a promising antibody-drug conjugate that targets HER2, showing a wider therapeutic window and reduced toxicity compared to traditional HER2-targeting treatments.

RC48 is being investigated for its effectiveness in various cancers, particularly gastric and gastroesophageal junction cancers, indicating its potential as a versatile treatment option in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disitamab vedotin, a novel HER2-directed antibody-drug conjugate in gastric cancer and other solid tumors. Hu, Y., Zhu, Y., Wei, X., et al.[2022]

RC48, an antibody-drug conjugate targeting HER2, combined with the antiangiogenic drug bevacizumab, showed significant efficacy in treating a 49-year-old woman with stage IV HER2-positive breast cancer and brain metastases, resulting in a partial response and 7 months of progression-free survival.

The treatment was well tolerated with no observed toxicities, highlighting the potential of combining ADCs with antiangiogenics as a promising strategy for managing metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disitamab Vedotin (RC48) combined with bevacizumab for treatment of HR-negative/HER2-positive metastatic breast cancer with liver and brain involvement: A case report. Qu, F., Liu, Q., Lu, R., et al.[2023]

Disitamab Vedotin (RC48) demonstrated effective and durable clinical responses in a 60-year-old woman with stage IV HER2-positive breast cancer, achieving significant tumor control after 12 cycles of treatment without severe adverse effects.

The patient had previously experienced disease progression despite multiple lines of therapy, highlighting RC48's potential as a viable third-line treatment option for patients with hormone receptor-positive and HER2-positive metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term remission under Disitamab Vedotin (RC48) in HR-positive/HER2-positive metastatic breast cancer with brain meningeal, and bone marrow involvement: A case report. Wu, Q., He, L., Luo, J., et al.[2022]

Disitamab vedotin (RC48), an HER2-targeted antibody-drug conjugate, shows enhanced tumor suppression and improved antitumor immunity when combined with PD-1/PD-L1 immune checkpoint inhibitors in a human HER2-expressing breast cancer model.

The combination therapy not only led to significant tumor rejection but also promoted the formation of immunological memory, providing long-lasting protection against tumor recurrence in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation. Huang, L., Wang, R., Xie, K., et al.[2022]

Tucatinib, at a recommended phase 2 dose of 300 mg twice daily, demonstrated acceptable safety with manageable side effects, including diarrhea and nausea, in a study of 60 patients with HER2-positive breast cancer.

The combination of tucatinib with capecitabine or trastuzumab showed promising anti-tumor activity, with an objective response rate of 83% for tucatinib plus capecitabine, indicating its potential as an effective treatment option for patients who have progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Murthy, R., Borges, VF., Conlin, A., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Disitamab Vedotin: First Approval. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Disitamab vedotin, a novel HER2-directed antibody-drug conjugate in gastric cancer and other solid tumors. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Disitamab Vedotin (RC48) combined with bevacizumab for treatment of HR-negative/HER2-positive metastatic breast cancer with liver and brain involvement: A case report. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Long-term remission under Disitamab Vedotin (RC48) in HR-positive/HER2-positive metastatic breast cancer with brain meningeal, and bone marrow involvement: A case report. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. [2022]