Tucatinib + Trastuzumab Deruxtecan for Breast Cancer

(HER2CLIMB-04 Trial)

Recruiting at 33 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

70 Participants Needed

Trial Summary

What is the purpose of this trial?

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 these drugs are given together. A side effect is anything a drug does besides treating cancer. Participants in this trial have HER2-positive (HER2+) breast cancer that has either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and T-DXd.

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.

What data supports the effectiveness of the drug Trastuzumab Deruxtecan for breast cancer?

Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer, especially in patients who have already tried other treatments. In studies, many patients with advanced breast cancer responded well to this drug, with some experiencing benefits for over 20 months. ^{1 2 3 4 5}

Is the combination of Tucatinib and Trastuzumab Deruxtecan safe for humans?

Trastuzumab Deruxtecan, also known as Enhertu or DS-8201a, has been shown to have a generally manageable safety profile in clinical trials for HER2-positive breast cancer. Common side effects include blood and stomach issues, and there is a risk of serious lung problems, so careful monitoring is needed. Tucatinib, known as Tukysa or ONT-380, is not specifically mentioned in the provided research, but it is often used in combination with other drugs for breast cancer treatment. ^{1 2 3 6 7}

What makes the drug combination of Tucatinib and Trastuzumab Deruxtecan unique for treating breast cancer?

The combination of Tucatinib and Trastuzumab Deruxtecan is unique because it targets HER2-positive breast cancer with a dual approach: Tucatinib is a small molecule inhibitor that specifically blocks the HER2 protein, while Trastuzumab Deruxtecan is an antibody-drug conjugate that delivers a potent chemotherapy directly to cancer cells, potentially improving effectiveness in patients who have already tried other HER2-targeted treatments. ^{1 2 3 5 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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 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]

References

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

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021]

2. England 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. [2020]

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

Trastuzumab Deruxtecan: First Approval. [2020]

4. England 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. [2023]

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

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023]

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

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. [2022]

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

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. [2020]