Tucatinib for Metastatic Breast Cancer

Recruiting at 6 trial locations

Overseen By Nelson Moss, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP2C8 inhibitors, CYP3A4 inducers

Disqualifiers: Allergy to tucatinib, Significant comorbidities, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study to see how the brain absorbs, distributes, and gets rid of tucatinib in people who have HER2+ cancers (breast cancer, NSCLC, CRC, or GEC) that have spread to the brain, and to learn more about how cancer cells develop resistance to treatment. The researchers will do research tests to look for genetic differences between HER2+ breast cancer that has spread to the brain and progressed during treatment with tucatinib and cancers that are being treated with tucatinib for the first time.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs that affect liver enzymes (CYP2C8 or CYP3A4) close to starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Tucatinib for metastatic breast cancer?

Tucatinib has been shown to be effective in treating advanced HER2-positive breast cancer, including cases with brain metastases. In a clinical trial, patients taking tucatinib with other drugs lived longer without their cancer getting worse compared to those who did not take tucatinib. ^{1 2 3 4 5}

Is tucatinib safe for humans?

Tucatinib has been studied for safety in humans, and important safety concerns include diarrhea and liver issues. It was approved by the FDA for use in combination with other drugs for advanced breast cancer, indicating a favorable balance between benefits and risks. ^{2 3 4 5 6}

How is the drug tucatinib unique for treating metastatic breast cancer?

Tucatinib is unique because it is an oral drug that selectively targets the HER2 protein, which is often overactive in certain breast cancers, and it has shown effectiveness in treating brain metastases, a common complication in HER2-positive breast cancer. ^{1 2 4 5 6}

Research Team

Andrew Seidman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with HER2+ cancers that have spread to the brain, able to swallow pills, and expected to live more than 12 weeks. They should not have decision-making impairments or significant other illnesses as judged by a doctor. Women must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

I have had multiple treatments for my condition.

I took lapatinib or neratinib over 6 months ago.

Life expectancy of >12 weeks

Exclusion Criteria

I am taking medication that interacts with certain enzymes and could cause serious side effects.

Significant medical co-morbidities as per investigator evaluation

I am not allergic to tucatinib or its ingredients.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Participants receive tucatinib at a standard dose of 300 mg orally twice daily for 4 days prior to surgery

4 days

Surgery

Participants undergo clinically indicated brain surgery to resect HER2+ brain metastases

1 day

Follow-up

Participants are monitored for safety and effectiveness after surgery and treatment

3 days

Post-operative Monitoring

Participants may continue tucatinib post-operatively at the discretion of the treating oncologist with monitoring as per clinical routine

Treatment Details

Interventions

• Tucatinib

Trial Overview The trial is testing how tucatinib behaves in the brain when treating HER2+ cancers that have metastasized there. It aims to understand drug distribution, elimination, and resistance development in patients undergoing surgery for these tumors.

Participant Groups

Group I: Patients with documented radiological and/or clinical CNS progression with no prior tucatinib Experimental Treatment 1 Intervention

Cohort B: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Group II: Patients already on Tucatinib Experimental Treatment 1 Intervention

Cohort A: This is a non-interventional study patients who will enter while already on Tucatinib . Patients in cohort A who are already on Tucatinib at a dose reduction (i.e., for toxicity) will continue the same dose.

Group III: HER2+ esophagogastric, lung, or colon cancer brain metastases and HER2 mutant breast cancer Experimental Treatment 1 Intervention

Cohort C: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Tucatinib is already approved in United States, European Union, Switzerland for the following indications:

Approved in United States as Tukysa for:

• Metastatic HER2-positive breast cancer
• RAS wild-type HER2-positive colorectal cancer

Approved in European Union as Tukysa for:

• HER2-positive locally advanced or metastatic breast cancer

Approved in Switzerland as Tukysa for:

• Metastatic HER2-positive breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Seagen Inc.

Industry 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

Findings from Research

In a phase I study involving 41 patients with HER2-positive brain metastases, the combination of tucatinib and trastuzumab was found to be tolerable, with a maximum tolerated dose of 300 mg twice daily or 750 mg once daily, and common side effects including elevated liver enzymes.

The treatment showed preliminary efficacy, with a clinical benefit rate of 35% in the twice-daily cohort and 53% in the once-daily cohort, indicating potential effectiveness in managing brain metastases in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases. Metzger Filho, O., Leone, JP., Li, T., et al.[2021]

In patients with HER2-positive metastatic breast cancer who had previously received multiple treatments, tucatinib combined with trastuzumab and capecitabine significantly improved progression-free survival at 1 year (33.1% vs. 12.3% for placebo) and overall survival at 2 years (44.9% vs. 26.6% for placebo).

Tucatinib was particularly effective for patients with brain metastases, showing a 1-year progression-free survival of 24.9% compared to 0% in the placebo group, although it was associated with higher rates of adverse events like diarrhea and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. Murthy, RK., Loi, S., Okines, A., et al.[2021]

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]

Tucatinib, approved by the FDA for advanced HER2-positive breast cancer, significantly improved progression-free survival (PFS) and overall survival (OS) compared to placebo, particularly benefiting patients with brain metastases, who comprised 48% of the study population.

The HER2CLIMB trial demonstrated a favorable benefit-risk profile for tucatinib, although it is associated with safety concerns such as diarrhea and hepatotoxicity, which are important to monitor during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Tucatinib for the Treatment of Patients with Advanced or Metastatic HER2-positive Breast Cancer. Shah, M., Wedam, S., Cheng, J., et al.[2022]

HER2 overexpression occurs in 15-20% of breast cancer cases and is associated with poor prognosis, making effective treatment crucial for these patients.

The FDA has approved tucatinib, a new tyrosine kinase inhibitor, which shows promise in combination with immunotherapy and chemotherapy for treating advanced HER2-positive breast cancer, addressing the challenge of resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer. Sirhan, Z., Thyagarajan, A., Sahu, RP.[2022]

Tucatinib is a selective HER2 inhibitor that has been approved for treating HER2-positive breast cancer in the USA and Switzerland, marking a significant advancement in targeted cancer therapy.

The drug was developed by Array BioPharma and Seattle Genetics, and its approval is based on its efficacy in patients with advanced unresectable or metastatic HER2-positive breast cancer, with further regulatory reviews pending in multiple countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib: First Approval. Lee, A.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. [2021]

3. 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]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Tucatinib for the Treatment of Patients with Advanced or Metastatic HER2-positive Breast Cancer. [2022]

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

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer. [2022]

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

Tucatinib: First Approval. [2021]