GDC-0084 + Trastuzumab for HER2-Positive Breast Cancer

Overseen By Jose P Leone, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Trastuzumab

Must not be taking: PI3K inhibitors, mTOR inhibitors

Disqualifiers: Visceral crisis, Leptomeningeal metastases, Uncontrolled illness, 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: 3

Duration: 24 weeks

47 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a drug called GDC-0084 as a possible treatment for HER2-Positive Breast Cancer. The drugs involved in this study are: * GDC-0084 * Trastuzumab (Herceptin®)

Will I have to stop taking my current medications?

The trial does not allow the use of other anti-cancer therapies during the study, but supportive care medications like pain relievers are allowed. If you are taking medications that strongly affect the enzyme CYP3A4, you may need to stop or switch them before starting the trial. No washout period is required for trastuzumab or endocrine therapy if you have been on ovarian suppression for at least 28 days.

What data supports the effectiveness of the drug combination GDC-0084 and trastuzumab for HER2-positive breast cancer?

Trastuzumab, a key drug for HER2-positive breast cancer, has been shown to improve survival rates when combined with other treatments. Although specific data on GDC-0084 is not provided, trastuzumab's effectiveness in similar combinations suggests potential benefits. ^{1 2 3 4 5}

Is the combination of GDC-0084 and Trastuzumab safe for humans?

Trastuzumab, also known as Herceptin and other names, is generally considered safe for humans, but it can cause side effects like lung issues (interstitial lung disease) and gastrointestinal problems. These side effects are usually manageable with careful monitoring and treatment adjustments. ^{6 7 8 9 10}

What makes the drug GDC-0084 + Trastuzumab unique for HER2-positive breast cancer?

The combination of GDC-0084, a drug that targets specific cancer cell growth pathways, with Trastuzumab, an antibody therapy that targets the HER2 protein, offers a novel approach by potentially enhancing the effectiveness of treatment for HER2-positive breast cancer, which is known for its aggressive nature. ^{3 11 12 13 14}

Research Team

Jose P Leone, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with HER2-positive breast cancer that has spread to the brain. They must have measurable brain metastasis, normal organ and marrow function, no prior treatments with certain inhibitors, and not be on strong CYP3A4 inducers or inhibitors. Pregnant women or those unable to swallow oral medication are excluded.

Inclusion Criteria

I can swallow and keep down pills.

I am 18 years old or older.

My disease is either not changing, absent, or getting worse.

Exclusion Criteria

You have had a bad reaction to trastuzumab in the past.

Current use or history of receiving a non-approved, investigational treatment within 14 days prior to initiation of protocol therapy

You cannot have an MRI due to a known medical reason.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GDC-0084 and Trastuzumab. GDC-0084 is administered orally once daily, and Trastuzumab is administered intravenously with a loading dose followed by maintenance doses every 3 weeks.

24 weeks

Every 3 weeks (in-person for Trastuzumab administration)

Surgical Intervention

Surgical brain metastasis resection for participants in Cohort B.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of response rates and survival.

2 years

Treatment Details

Interventions

• GDC-0084
• Trastuzumab

Trial Overview The study tests GDC-0084 in combination with Trastuzumab (Herceptin®) as a treatment for patients with HER2-positive breast cancer that has metastasized to the brain. It aims to see how well these drugs work together in this specific patient group.

Participant Groups

Group I: Cohort B: a pre-surgical window cohort Experimental Treatment 2 Interventions

GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter Surgical brain metastasis resection

Group II: Cohort A: single-arm, two stage, phase II cohort Experimental Treatment 2 Interventions

GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Kazia Therapeutics Limited

Industry Sponsor

Trials

12

Recruited

1,600+

Findings from Research

Trastuzumab (Herceptin) has demonstrated significant antitumor activity in patients with HER-2-positive metastatic breast cancer, improving response and survival rates when combined with first-line chemotherapy.

Recent clinical trials have focused on new chemotherapy approaches for node-positive breast cancer, laying the groundwork for ongoing studies that incorporate trastuzumab into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. Perez, EA., Hortobagyi, GN.[2015]

In the phase 2 DESTINY-Breast01 trial, trastuzumab deruxtecan (T-DXd) showed a remarkable objective response rate of 60.9% and a median progression-free survival of 16.4 months in HER2+ metastatic breast cancer patients, supporting its use after multiple prior treatments.

While T-DXd is effective, it has a notable side effect of pneumonitis occurring in 13.6% of patients, leading to warnings for interstitial lung disease and embryo-fetal toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for HER2+ advanced breast cancer. Lee, J., Park, YH.[2022]

Trastuzumab deruxtecan (T-DXd) has shown effectiveness in treating HER2-low breast cancer, indicating its potential as a targeted therapy for this subtype.

This finding highlights the importance of developing treatments that can specifically target and benefit patients with lower levels of HER2 expression, expanding options for breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan Is Effective in HER2-Low Breast Cancer. [2021]

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]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

The anti-HER3 antibody in combination with trastuzumab exerts synergistic antitumor activity in HER2-positive gastric cancer. [2017]

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

Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer. [2018]

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Ongoing and planned adjuvant trials with trastuzumab. [2015]

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

Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. [2022]

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

Trastuzumab deruxtecan for HER2+ advanced breast cancer. [2022]

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

Trastuzumab Deruxtecan Is Effective in HER2-Low Breast Cancer. [2021]

8. France pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2-positive gastric cancer. [2023]

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

Trastuzumab in combination with heregulin-activated Her-2 (erbB-2) triggers a receptor-enhanced chemosensitivity effect in the absence of Her-2 overexpression. [2015]

12. Greece pubmed.ncbi.nlm.nih.gov

Antibody therapy for breast cancer. [2015]

13. England pubmed.ncbi.nlm.nih.gov

Controversies in the use of adjuvant trastuzumab (Herceptin). [2015]

14. France pubmed.ncbi.nlm.nih.gov

[Indications for Herceptin in breast cancer treatment]. [2015]