Disitamab Vedotin + Tucatinib for Breast Cancer

Recruiting at 162 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seagen Inc.

Must not be taking: ADCs, Tucatinib

Disqualifiers: Active CNS metastasis, Other malignancy, 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: Unknown

172 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced breast or gastric cancer that contains the HER2 protein, which promotes cancer growth and spread. The combination includes disitamab vedotin, an experimental drug designed to target and kill cancer cells, and tucatinib, a drug already approved for cancer treatment. The trial aims to assess the safety and effectiveness of this combination and identify any side effects. Individuals with difficult-to-treat breast or gastric cancer who have already tried other therapies might be suitable for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that disitamab vedotin, a drug targeting HER2, has delivered promising results in cancer treatment. It has been tested alone and with tucatinib. Together, they demonstrate strong antitumor activity, effectively fighting cancer.

Patients generally tolerate disitamab vedotin well, with most not experiencing severe side effects. However, like all cancer treatments, side effects such as nausea or fatigue can occur.

Tucatinib is already approved for cancer treatment in the United States, indicating prior safety testing in other conditions.

Researchers are studying the combination of disitamab vedotin and tucatinib to assess their effectiveness against advanced cancers. The current study is in Phase 2, providing some safety information, but more research is needed to fully understand its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Disitamab Vedotin is unique because it combines a novel antibody-drug conjugate with tucatinib, specifically targeting HER2-positive cancer cells. This approach allows for more precise delivery of chemotherapy directly to the cancer cells, potentially reducing harm to healthy cells. Unlike traditional chemotherapy that affects both healthy and cancerous cells, Disitamab Vedotin focuses on HER2 receptors found in certain breast cancer types, which might lead to more effective and less toxic treatment. Researchers are excited because this targeted mechanism could offer improved outcomes for patients with fewer side effects compared to existing treatments.

What evidence suggests that disitamab vedotin and tucatinib could be effective for advanced or metastatic breast cancer?

Research has shown that disitamab vedotin, a targeted cancer treatment, is effective for patients with HER2-positive and HER2-low breast cancer. One study found that about one-third of patients experienced tumor shrinkage, and 81.97% had their disease either improve or remain stable. In this trial, participants will receive a combination of disitamab vedotin and tucatinib, which has demonstrated even better results, particularly for those with HER2-low tumors. Tucatinib already has approval for treating certain cancers, supporting its effectiveness. These findings suggest that this combination could benefit people with advanced breast or stomach cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Disitamab Vedotin
• Tucatinib

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12408859/

Disitamab Vedotin in HER2-Positive and HER2-Low Breast ... Notably, combination therapy significantly improved outcomes in HER2-low patients. Keywords: Disitamab vedotin, antibody-drug conjugates, real-world study, ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO1-04-07/743518/Abstract-PO1-04-07-Disitamab-vedotin-a-clinical

Abstract PO1-04-07: Disitamab vedotin, a clinical stage HER2 ... Disitamab vedotin, a clinical stage HER2-directed antibody-drug conjugate, shows potent antitumor activity as a monotherapy and in combination with tucatinib ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06157892

NCT06157892 | A Study of Disitamab Vedotin With Other ... This clinical trial is to evaluate disitamab vedotin in combination with tucatinib in subjects with LA/metastatic breast cancer or gastric cancer/GEJC that ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13022

Effectiveness and safety of disitamab vedotin (RC48) in ... RC48 showed a promising antitumor activity and acceptable tolerability in this pretreated patient population with HER2-positive ABC.

5. onclive.com onclive.com/view/disitamab-vedotin-shows-early-efficacy-in-her2-expressing-breast-cancer-with-pam-pathway-abnormalities

Disitamab Vedotin Shows Early Efficacy in HER2- ... Disitamab vedotin demonstrated a 34.40% objective response rate and 81.97% disease control rate in HER2-expressing metastatic breast cancer with ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-of-disitamab-vedotin-and-tucatinib-for-patients-with-advanced-breast-cancer-or-gastric-cancer/

Study of Disitamab Vedotin and Tucatinib for Patients with ... The study will explore how these treatments work in different groups of patients, including those with HER2-low and HER2-positive breast cancer, ...