Tucatinib + Trastuzumab Deruxtecan for Breast Cancer

(HER2CLIMB-04 Trial)

No longer recruiting at 162 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: Lapatinib, Neratinib, Tucatinib, others

Disqualifiers: Cardiopulmonary disease, Hepatitis B, Hepatitis C, 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

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the combination of the drugs tucatinib and trastuzumab deruxtecan treats HER2-positive breast cancer that has spread or cannot be removed by surgery. Researchers aim to determine the effectiveness of these drugs together and identify potential side effects. Participants should have HER2-positive breast cancer that has spread or is not surgically removable and must have previously tried treatments like taxane and trastuzumab. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had any systemic anti-cancer therapy within 21 days before starting the trial, except for certain hormonal therapies. It's best to discuss your current medications with the trial team.

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

Research shows that trastuzumab deruxtecan (T-DXd) is generally safe and effective for treating breast cancer. In real-world studies, T-DXd has produced better results than some other treatments. However, like any cancer drug, it can cause side effects. Common side effects include nausea and a reduction in white blood cells, which may increase infection risk.

Tucatinib, another drug used in this combination, is also considered safe. Past studies have successfully used it for HER2-positive breast cancer. Some patients have reported mild side effects such as diarrhea and fatigue.

Both drugs have approval for treating certain types of breast cancer, indicating they have passed safety checks for those uses. This trial, however, examines their combined use, so monitoring for any new side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tucatinib and Trastuzumab Deruxtecan for breast cancer because it offers a novel approach to treatment. Unlike standard options like Trastuzumab or Pertuzumab, which primarily inhibit HER2 receptors, this combined treatment targets cancer cells more precisely. Trastuzumab Deruxtecan is an antibody-drug conjugate that delivers chemotherapy directly inside the cancer cells, while Tucatinib enhances this effect by specifically blocking HER2 signals. This dual-action mechanism could potentially lead to more effective treatments with fewer side effects, offering hope for patients with HER2-positive breast cancer.

What evidence suggests that tucatinib and trastuzumab deruxtecan could be effective for HER2-positive breast cancer?

Research has shown that combining tucatinib and trastuzumab deruxtecan (T-DXd) may effectively treat HER2-positive breast cancer. In real-world studies, T-DXd has outperformed some other treatments for patients with advanced stages of the disease. Tucatinib-based treatments have also demonstrated good results, particularly for patients with cancer that has spread to the brain. This trial will evaluate the combination of tucatinib and T-DXd, potentially offering a strong option for those with HER2-positive breast cancer that has spread or cannot be removed. ^{1 3 4 6 7}

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 people with HER2+ breast cancer that's spread or can't be fully removed by surgery. They should have had prior treatment with a taxane and trastuzumab, measurable disease, and treated brain metastases if present. Excluded are those who've recently used certain drugs like Lapatinib, have serious heart or lung conditions, active infections, liver diseases, or can't take pills.

Inclusion Criteria

My brain scans show stable or treated brain metastases.

I was treated with taxane and trastuzumab for my cancer and it either didn't work or my cancer returned within 6 months.

I have brain metastases that don't require immediate treatment.

Exclusion Criteria

I am currently taking tucatinib or am enrolled in a tucatinib trial.

I was treated with Lapatinib or neratinib less than a year ago, but not for disease progression or severe side effects.

I have never taken experimental drugs for HER2 or EGFR.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tucatinib in combination with trastuzumab deruxtecan

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab Deruxtecan
• Tucatinib

Trial Overview The study tests how well tucatinib works alongside trastuzumab deruxtecan (T-DXd) in treating HER2+ breast cancer. All participants will receive both medications to see their effectiveness and monitor any side effects when combined.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 2 Interventions

Tucatinib + trastuzumab deruxtecan

Trastuzumab Deruxtecan is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Approved in United States as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
• HER2-low breast cancer

Approved in Japan as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

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

Published Research Related to This Trial

In the TUXEDO-1 trial involving 15 patients with HER2-positive breast cancer and brain metastases, trastuzumab deruxtecan achieved a high overall intracranial response rate of 73.3%, indicating its efficacy in treating this challenging condition.

The treatment was well-tolerated, with no new safety concerns reported, and patients maintained their quality of life and cognitive functioning throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Bartsch, R., Berghoff, AS., Furtner, J., et al.[2022]

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

In the phase 3 DESTINY-Breast02 trial involving 608 patients with HER2-positive metastatic breast cancer, trastuzumab deruxtecan significantly improved median progression-free survival to 17.8 months compared to 6.9 months for treatment of physician's choice, demonstrating its efficacy in a population with limited treatment options.

While trastuzumab deruxtecan had a higher incidence of treatment-emergent adverse events, including nausea and interstitial lung disease, it still showed a favorable benefit-risk profile, indicating its potential as a viable treatment option for patients resistant to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. André, F., Hee Park, Y., Kim, SB., et al.[2023]

In a phase 2 study involving 184 patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a significant response rate of 60.9%, with a median response duration of 14.8 months.

While trastuzumab deruxtecan showed promising efficacy, it was associated with notable adverse effects, including interstitial lung disease in 13.6% of patients, highlighting the need for careful monitoring of pulmonary symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. Modi, S., Saura, C., Yamashita, T., et al.[2021]

In a phase 1 trial involving 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer, trastuzumab deruxtecan demonstrated a manageable safety profile, with the most common serious side effects being anemia and decreases in blood cell counts, but no drug-related deaths were reported.

The treatment showed promising preliminary activity, with 43.2% of patients achieving a confirmed objective response, indicating its potential effectiveness in patients who had previously been treated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Shitara, K., Iwata, H., Takahashi, S., et al.[2020]

Trastuzumab deruxtecan (ENHERTU®) is an innovative treatment that combines an antibody targeting HER2 with a DNA topoisomerase I inhibitor, specifically designed for HER2-expressing solid tumors, including various types of cancer.

It received accelerated approval in the USA based on the promising results from the phase 2 DESTINY-Breast01 trial, which focused on patients with advanced HER2-positive breast cancer who had already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. Keam, SJ.[2020]

In a phase 1 trial involving 115 patients with HER2-positive breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a manageable safety profile, with 59.5% of patients achieving a confirmed objective response.

Despite some serious treatment-emergent adverse events, including cases of interstitial lung disease and pneumonitis, the preliminary efficacy results suggest that trastuzumab deruxtecan is a promising treatment option, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Tamura, K., Tsurutani, J., Takahashi, S., et al.[2020]

Citations

1. 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 ...

2. onclive.com onclive.com/view/real-world-data-support-tucatinib-based-treatment-in-her2-metastatic-breast-cancer

Real-World Data Support Tucatinib-Based Treatment in ... Tucatinib-based treatments showed effectiveness in HER2-positive metastatic breast cancer, including brain metastases and post-T-DXd treatment ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1030

Efficacy of tucatinib, trastuzumab, and capecitabine (TTC) ... This large retrospective cohort with extended follow-up highlights the efficacy of TTC in HER2-positive MBC patients previously treated with T-DXd.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04539938

NCT04539938 | A Study of Tucatinib Plus Trastuzumab ... This trial studies how well the drug tucatinib works when given with trastuzumab deruxtecan (T-DXd). It will also look at what side effects happen when ...

5. 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- ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40989560/

Real-world efficacy and safety of trastuzumab deruxtecan ... Interpretation: 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. clinicaltrialsarena.com clinicaltrialsarena.com/news/pfizer-tukysa-phase-iii-her2-breast-cancer-maintenance-trial/

Pfizer touts Tukysa in front-line breast cancer after Phase III ... Pfizer's TKI, Tukysa, has offered improvements to PFS in the maintenance setting during a Phase III trial in HER2+, metastatic breast cancer.