Tucatinib + Trastuzumab + Pertuzumab for Breast Cancer

(HER2CLIMB-05 Trial)

Recruiting at 560 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must be taking: Trastuzumab, Pertuzumab, Taxane

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Symptomatic brain metastasis, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 18 months

650 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in. All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have previously been treated with certain drugs like tucatinib or other similar medications targeting HER2 or EGFR.

What data supports the effectiveness of the drug combination of Tucatinib, Trastuzumab, and Pertuzumab for breast cancer?

Research shows that Pertuzumab and Trastuzumab, when used together, can significantly improve survival rates in patients with HER2-positive metastatic breast cancer. They work by blocking the HER2 protein, which helps slow down the growth of cancer cells. ^{1 2 3 4 5}

Is the combination of Tucatinib, Trastuzumab, and Pertuzumab safe for humans?

The combination of Trastuzumab and Pertuzumab has been studied for safety in breast cancer treatment, with some concerns about heart-related side effects. Pertuzumab's safety is continuously monitored, and it has been associated with adverse events, but it is generally considered safe when used as directed in clinical settings. ^{2 3 6 7 8}

How is the drug combination of Tucatinib, Trastuzumab, and Pertuzumab unique for treating breast cancer?

This drug combination is unique because it targets the HER2 protein in breast cancer cells more comprehensively by using three different drugs that bind to different parts of the HER2 receptor, potentially improving treatment effectiveness compared to using fewer drugs. ^{1 2 3 5 7}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for individuals with HER2-positive breast cancer that's locally advanced, unresectable, or metastatic. Participants should have received specific induction therapy without disease progression and can't be undergoing certain treatments or have poorly controlled seizures. They must not need immediate treatment for brain metastases and should not have symptomatic brain lesions posing risk.

Inclusion Criteria

My cancer cannot be removed by surgery and has spread.

My breast cancer is HER2 positive as per the latest guidelines.

I have had brain metastases treatment and currently have no symptoms.

Exclusion Criteria

I experience seizures more than once a week or have ongoing neurological symptoms.

I haven't taken specific cancer drugs like pyrotinib or lapatinib recently, except for neratinib over a year ago.

I have or might have cancer spread to the lining of my brain and spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tucatinib or placebo in combination with trastuzumab and pertuzumab every 21 days

Up to approximately 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Through 30 days after last study treatment

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to approximately 5 years

Treatment Details

Interventions

• Pertuzumab
• Placebo
• Trastuzumab
• Tucatinib

Trial Overview The study tests if tucatinib plus trastuzumab and pertuzumab is more effective than a placebo combined with the same drugs in treating HER2-positive breast cancer. It's randomized and blinded, meaning participants won't know if they're receiving tucatinib or a placebo.

Participant Groups

Group I: Tucatinib + trastuzumab + pertuzumab Experimental Treatment 4 Interventions

Tucatinib + trastuzumab + pertuzumab

Group II: Placebo + trastuzumab + pertuzumab Active Control 4 Interventions

Placebo + trastuzumab + pertuzumab

Pertuzumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in United States as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Canada as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Japan as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Pertuzumab is an effective anti-HER2 monoclonal antibody that works by preventing HER2 from forming heterodimers, which reduces tumor cell growth and survival, particularly in HER2-positive metastatic breast cancer.

In the phase III CLEOPATRA trial involving a combination of pertuzumab, trastuzumab, and docetaxel, patients experienced significantly improved progression-free survival and overall survival compared to those receiving placebo, with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer. McCormack, PL.[2021]

Pertuzumab, a new monoclonal antibody targeting HER2, has shown improved patient outcomes in clinical trials for early-stage and metastatic HER2-positive breast cancer, especially when used in combination with chemotherapy and trastuzumab.

The review highlights that while trastuzumab has improved survival for HER2-positive breast cancer, there is still a need for better treatment options, which pertuzumab aims to address, particularly for patients who continue to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. Lamond, NW., Younis, T.[2021]

In a phase IIa study involving 30 patients with advanced gastric cancer, the combination of pertuzumab and trastuzumab showed a well-tolerated safety profile, with partial responses in 86% of patients receiving a specific dosing regimen.

The pharmacokinetics indicated that the serum concentration of pertuzumab was lower in this gastric cancer population compared to those with metastatic breast cancer, leading to the selection of the 840 mg q3w dose for further phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Kang, YK., Rha, SY., Tassone, P., et al.[2021]

In a study of 266 patients with HER2-positive metastatic breast cancer, the majority received a treatment regimen of trastuzumab, pertuzumab, and a taxane, which aligns with the standard first-line therapy.

The median progression-free survival (PFS) for patients was 16.9 months, and the safety profile, including common side effects like fatigue and diarrhea, was consistent with findings from the pivotal CLEOPATRA trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes. Robert, NJ., Goertz, HP., Chopra, P., et al.[2020]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

Pertuzumab, a monoclonal antibody targeting HER2, significantly improves progression-free survival in patients with HER2-positive metastatic breast cancer, with a median of 18.5 months compared to 12.4 months for the placebo group, based on a phase III trial with previously untreated patients.

While the overall safety profile of pertuzumab is similar to placebo, it is associated with a higher incidence of specific side effects such as diarrhea, rash, and neutropenia, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Boix-Perales, H., Borregaard, J., Jensen, KB., et al.[2023]

A comprehensive analysis of 14,707 adverse events related to pertuzumab from the FDA Adverse Event Reporting System revealed significant safety concerns, including potential risks of myelosuppression, cardiotoxicity, and other serious conditions occurring in 12 organ systems.

Most adverse events, particularly cardiac-related issues, were reported within the first month of therapy, highlighting the need for careful monitoring and preparedness for emergency interventions, especially in elderly patients and those with pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). Zou, SP., Yang, HY., Ouyang, ML., et al.[2023]

References

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

Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer. [2021]

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

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes. [2020]

5. France pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

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

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). [2023]