Tucatinib for Metastatic Breast Cancer

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Andrew Seidman, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP2C8 inhibitors, CYP3A4 inducers

Disqualifiers: Allergy to tucatinib, Significant comorbidities, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 4 Jurisdictions

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}

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.

Trial 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 (Kinase Inhibitor)

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, Australia, 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 Australia as Tukysa for:

• Advanced unresectable or metastatic HER2-positive breast cancer

🇨🇭 Approved in Switzerland as Tukysa for:

• Metastatic HER2-positive breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Memorial Sloan Kettering Monmouth (Limited Protocol Activities) Middletown, NJ

Memorial Sloan Kettering Westchester (Limited Protocol Activities) Harrison, NY

Memorial Sloan Kettering Nassau (Limited Protocol Activities) Uniondale, NY

Memorial Sloan Kettering Bergen (Limited Protocol Activities) Montvale, NJ

More Trial Locations

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center Lead Sponsor

Pfizer Industry Sponsor

Seagen Inc. Industry Sponsor

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] Brain metastases are frequent in HER2-positive breast cancer. ONT-380 (tucatinib) is a potent selective inhibitor of HER2 with intracranial activity in preclinical models.

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

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. [2021] Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase.

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] Tucatinib is a potent and selective oral HER2 tyrosine kinase inhibitor, with the potential to provide a well tolerated new treatment option for patients whose disease has progressed on currently available therapies. We aimed to determine the recommended phase 2 dose, safety, pharmacokinetics, and preliminary activity of tucatinib in combination with capecitabine or trastuzumab in patients with HER2-positive breast cancer with or without brain metastases.

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] On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. This was the first new molecular entity evaluated under Project Orbis, an FDA Oncology Center of Excellence initiative, which supports concurrent review of oncology drugs by multiple global health authorities. Approval was based on the HER2CLIMB trial, which randomized patients to receive tucatinib or placebo with trastuzumab and capecitabine. Tucatinib demonstrated efficacy compared with placebo in progression-free survival [PFS; HR: 0.54; 95% confidence interval (CI): 0.42-0.71; P < 0.00001] and overall survival (OS; HR: 0.66; 95% CI, 0.50-0.87; P = 0.00480). Patients with either treated and stable or active brain metastases made up 48% of the study population. PFS in patients with brain metastases confirmed benefit (HR: 0.48; 95% CI, 0.34-0.69; P < 0.00001). The benefit in patients with brain metastases allowed for inclusion of this specific population in the indication. Important safety signals included diarrhea and hepatotoxicity which are listed under Warnings and Precautions. This article summarizes the FDA thought process and data supporting the favorable benefit-risk profile and approval of tucatinib.

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

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer. [2022] Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15-20% of breast cancer cases. HER2 is a member of the epidermal growth factor receptor (EGFR) family with tyrosinase kinase activity, and its overexpression is linked to poor prognosis and shorter progression-free survival (PFS) and overall survival (OS). Among various treatment options, HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors (TKIs) have mostly been applied in recent decades to treat HER2-positive (HER2+) breast cancer patients. Although positive clinical outcomes were documented in both advanced disease and neoadjuvant settings, the development of resistance mechanisms to such approaches has been one of the major challenges with the continuous usage of these drugs. In addition, patients who experience disease progression after treatment with multiple HER2-targeted therapies often have limited treatment options. The Food and Drug Administration (FDA) has recently approved a new TKI (i.e., tucatinib) for use in combination with immunotherapy and/or chemotherapeutic agents for the treatment of advanced-stage/metastatic HER2+ breast cancer. This review highlights recent updates on the efficacy of tucatinib-based therapeutic approaches in experimental models as well as in the clinical settings of HER2+ breast cancer.

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

Tucatinib: First Approval. [2021] Tucatinib is an oral, small molecule, selective HER2 inhibitor initially developed by Array BioPharma (a subsidiary of Pfizer) and subsequently developed by Seattle Genetics for the treatment of HER2-positive solid tumours, including breast cancer and colorectal cancer. Tucatinib was approved in the USA in April 2020 and in Switzerland in May 2020 for the treatment of HER2-positive breast cancer, and is pending regulatory review in the EU, Australia, Canada and Singapore. This article summarizes the milestones in the development of tucatinib leading to this first approval in patients with advanced unresectable or metastatic HER2-positive breast cancer.