Tucatinib + Trastuzumab + Pertuzumab for Breast Cancer

(HER2CLIMB-05 Trial)

Not currently recruiting at 660 trial locations

Overseen By Jane Meisel

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding tucatinib to standard treatments (trastuzumab and pertuzumab) is more effective than a placebo for treating HER2-positive breast cancer that cannot be surgically removed or has metastasized. It also examines potential side effects of this drug combination. Participants will randomly receive either tucatinib or a placebo, along with trastuzumab and pertuzumab. Those with HER2-positive breast cancer that is locally advanced or metastatic, who have completed specific initial therapies without disease progression, might be suitable for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

A study found that combining tucatinib with trastuzumab and pertuzumab was manageable for patients, with side effects mostly as expected. Diarrhea was a common side effect. Research showed that tucatinib, when used with other drugs, significantly shrank tumors. This indicates the treatment is suitable for most people. However, as with any treatment, side effects can occur, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of tucatinib with trastuzumab and pertuzumab for breast cancer because it introduces a new layer of precision in targeting the HER2 protein, which is often overexpressed in aggressive forms of this cancer. Tucatinib is unique because it specifically targets the HER2 protein, potentially leading to more effective treatment with fewer side effects compared to broader therapies. This specificity is expected to enhance the efficacy of the existing trastuzumab and pertuzumab duo, offering a promising new option for patients who may not respond to current standard treatments. By adding tucatinib, the treatment aims to improve outcomes and expand the arsenal against HER2-positive breast cancer.

What evidence suggests that tucatinib might be an effective treatment for HER2-positive breast cancer?

Research has shown that tucatinib, when combined with trastuzumab and pertuzumab, holds promise for treating HER2-positive breast cancer. In this trial, some participants will receive this combination. Studies have found that it can significantly extend the time patients live without their cancer worsening. Tucatinib targets HER2, a protein that accelerates cancer cell growth. In previous treatments, adding tucatinib after other HER2 therapies effectively helped patients with advanced breast cancer. This suggests tucatinib could be a strong option for those with metastatic or locally advanced breast cancer that cannot be surgically removed. Meanwhile, other participants in this trial will receive a placebo alongside trastuzumab and pertuzumab to compare the treatments' effectiveness. ^{2 4 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/tukysa-combination-significantly-improves-progression-free

TUKYSA Combination Significantly Improves Progression ... Treatment with TUKYSA in combination with trastuzumab and pertuzumab was tolerable, with a safety profile generally consistent with the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12035061/

Real-World Clinical Outcomes in Patients With HER2+ ... Tucatinib administered after ≥2 HER2-targeted therapies in the metastatic setting is an effective treatment option in patients with HER2 + MBC, including those ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05132582

NCT05132582 | A Study of Tucatinib or Placebo With ... 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.

4. nature.com nature.com/articles/s41591-024-03462-0

Tucatinib and trastuzumab in HER2-mutated metastatic ... An open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2- ...

5. facingourrisk.org facingourrisk.org/XRAY-tabs/combining-anti-HER2-drugs-improves-outcomes/printable

Combining two anti-HER2 drugs improves outcomes ... This study evaluates the safety and efficacy of combining the drugs tucatinib, trastuzumab and eribulin in patients with unresectable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12451362/

Real-world efficacy and safety of trastuzumab deruxtecan ... In this real-world study, T-DXd was more effective than T-DM1 as a second-line treatment and tucatinib as a third-line treatment, in line with ...

7. tukysa.com tukysa.com/mbc/what-is-tukysa

About TUKYSA® (tucatinib) for HER2+ MBC - Safety Info The most common side effects of TUKYSA in combination with trastuzumab and capecitabine in adults with HER2-positive breast cancer include: • diarrhea.

8. conference-correspondent.com conference-correspondent.com/highlights/sabcs/results-from-the-i-spy-2-trial-of-tucatinib-plus-paclitaxel-pertuzumab-trastuzumab-followed-by-doxorubicin-cyclophosphamide-in-high-risk-her2-positive-stage-ii-iii-breast-cancer

Results from the I-SPY 2 Trial of Tucatinib plus Paclitaxel + ... Tucatinib-containing therapy resulted in a tumor volume reduction of >80%. Tucatinib was found to be highly effective when combined with paclitaxel plus ...