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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, GDC-0084 (an experimental treatment) and Trastuzumab, to determine their effectiveness in treating HER2-positive breast cancer, particularly when it has spread to the brain. The study aims to assess whether this combination can control cancer growth in patients with brain metastases. Candidates for this study include individuals with HER2-positive breast cancer and evidence of brain tumors, especially those who have undergone certain treatments or require brain surgery. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that trastuzumab is a well-known treatment for HER2-positive breast cancer. It has been used for many years and is generally safe. Some patients might experience side effects like fever or chills, but these are usually manageable.

GDC-0084 is a newer drug under study. Researchers are examining its effectiveness with trastuzumab in treating cancer. This study is in a mid-stage trial, indicating that earlier research found the drug safe enough for further testing. However, specific information about its safety when combined with trastuzumab is still being collected.

The combination is closely monitored to understand its effects on patients and ensure safety. Researchers watch participants for any side effects to maintain safety during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GDC-0084 combined with Trastuzumab because this duo targets HER2-positive breast cancer in a novel way. Unlike standard treatments that primarily target the HER2 protein, GDC-0084 is a PI3K inhibitor, which means it blocks a pathway that cancer cells use to grow and survive. This dual approach not only attacks cancer from two different angles but also holds promise for more effectively treating brain metastases, a challenging complication in breast cancer. The combination of an oral treatment (GDC-0084) and an established intravenous therapy (Trastuzumab) offers a comprehensive strategy that could improve outcomes for patients with this aggressive cancer type.

What evidence suggests that GDC-0084 and Trastuzumab could be effective for HER2-Positive Breast Cancer?

Research has shown that trastuzumab improves survival rates in HER2-positive breast cancer when combined with other treatments. Studies have found that combining trastuzumab with additional drugs can better manage the disease. In this trial, participants will receive a combination of trastuzumab and GDC-0084, a new drug being tested for its potential to treat HER2-positive breast cancer, particularly when the cancer has metastasized to the brain. Early findings suggest that GDC-0084 might enhance the effects of trastuzumab, making this combination promising. Although further research is necessary, these early results offer hope for improved treatment options. ^{2 3 4 6 7}

Who Is on the Research Team?

Jose P Leone, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

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

I have brain metastases, haven't had brain radiation, and don't need steroids for symptoms.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03765983

Study Details | NCT03765983 | GDC-0084 in Combination ... This research study is studying a drug called GDC-0084 as a possible treatment for HER2-Positive Breast Cancer.

2. withpower.com withpower.com/trial/phase-3-brain-neoplasms-1-2019-3fb75

GDC-0084 + 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 ...

3. cancertherapyadvisor.com cancertherapyadvisor.com/home/cancer-topics/breast-cancer/breast-cancer-brain-metastases-gdc0084-trastuzumab/

Clinical Trial: GDC-0084 Plus Trastuzumab in HER2+ ... Researchers are studying GDC-0084 plus trastuzumab in patients with HER2-positive breast cancer and brain metastases.

4. youtube.com youtube.com/watch?v=kjI1EN5de2o

Study of GDC-0084 with Trastuzumab in HER2-Positive ... Jose Pablo Leone, MD, provides an overview of a study of PI3K inhibitor GDC-0084 with trastuzumab in patients with HER2-positive breast ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/cnr2.1274

HER2‐positive breast cancer brain metastasis: A new and ... Phase II trial of GDC-0084 in combination with trastuzumab for patients with HER2-positive breast cancer brain metastases, Trastuzumab + GDC- ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT03765983

GDC-0084 in Combination With Trastuzumab for Patients With ... In this research study, the investigators are looking to see how your cancer responds to the combination of GDC-0084 and Trastuzumab.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11693720/

The multidisciplinary management of HER2-positive breast ... Trastuzumab and pertuzumab are FDA-approved HER2-targeted monoclonal antibodies (mAbs) used to manage metastatic HER2-positive breast cancer.