What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as targeted therapies, ADCs, and TKIs, often come with a range of side effects. Targeted therapies like CDK4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib) can cause neutropenia, fatigue, and gastrointestinal issues. ADCs, such as trastuzumab-deruxtecan, may lead to nausea, fatigue, and potential cardiotoxicity. TKIs, including lapatinib and neratinib, are associated with diarrhea, liver toxicity, and skin rashes. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that align with the mechanisms being studied in the trial. Notable targeted therapies include cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) such as palbociclib, ribociclib, and abemaciclib, which are used for ER-positive, HER2-negative breast cancer. For HER2-positive breast cancer, antibody-drug conjugates (ADCs) like ado-trastuzumab emtansine and trastuzumab deruxtecan, as well as tyrosine kinase inhibitors (TKIs) such as tucatinib, lapatinib, pyrotinib, and neratinib, have been approved. These treatments have shown efficacy in various settings, including after progression on prior therapies.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) Targeted therapies like PI3K inhibitors (e.g., alpelisib) for PIK3CA-mutated, HR-positive, HER2-negative breast cancer. 2) Antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan for HER2-positive breast cancer, which has shown significant efficacy in patients with prior treatment. 3) Tyrosine kinase inhibitors (TKIs) like tucatinib, which, when combined with trastuzumab and capecitabine, have demonstrated improved outcomes in HER2-positive metastatic breast cancer. These treatments offer new mechanisms of action and have shown promising results in clinical trials.

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Cyclin-dependent kinase 4/6 inhibitor

Combination Therapy for Breast Cancer

Phase 1 & 2

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Postmenopausal status for women

Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease (note: at least one line of therapy must have contained a CDK4/6i administered for a minimum of 8 weeks prior to disease progression.)

Must not have

Receipt of a live-virus vaccination within 28 days or less of planned treatment start

Active bleeding diatheses

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing new treatments for advanced breast cancer in patients whose cancer has not responded to previous treatments. It aims to find more effective drug combinations for these patients. One of the treatments being tested is Lapatinib, which is being evaluated both for patients whose cancer has returned and as an initial treatment option in combination with chemotherapy.

Who is the study for?

This trial is for postmenopausal women with advanced or metastatic ER-positive, HER2-negative breast cancer that worsened after CDK4/6 inhibitor treatment. It's also for those with ER-positive, HER2-positive breast cancer resistant to anti-HER2 therapies and trastuzumab-and-taxane-based therapy. Participants must have a life expectancy of at least 3 months and be able to provide a tumor sample.

What is being tested?

The study tests various drug combinations (like Atezolizumab, Palbociclib) in two cohorts based on the type of breast cancer. Patients are randomly assigned to different treatments which may change if they experience disease progression or unacceptable side effects during the initial stage.

What are the potential side effects?

Potential side effects include allergic reactions to drugs or their components, organ inflammation, infection risks due to immune system suppression by some treatments, blood sugar level changes possibly requiring diabetes management, and general symptoms like fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a woman and have gone through menopause.

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My cancer worsened after hormone therapy including a CDK4/6 inhibitor.

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I am advised to undergo hormone therapy for my condition, not chemotherapy.

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My breast cancer has worsened after the last treatment.

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My breast cancer is advanced and cannot be removed with surgery.

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My tumor is estrogen receptor-positive.

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I am fully active or can carry out light work.

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My breast cancer is ER-positive and HER2-positive.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not received a live-virus vaccine in the last 28 days.

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I currently have a bleeding disorder.

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I have symptoms of lung disease, such as trouble breathing.

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I have diabetes and need insulin.

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I have high calcium levels in my blood that are causing symptoms.

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I have a history of cancer.

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I have had eye inflammation or infections, or a history of uveitis.

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I haven't had breast cancer treatment in the last 2 weeks or within 5 half-lives of the drug.

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I have a digestive issue that affects how my body absorbs medication.

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I have not taken drugs targeting the PI3K/Akt/mTOR pathway.

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I have a lung condition that makes it hard to breathe without help.

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I have had major surgery on my stomach or small bowel, or I have a chronic condition causing frequent severe diarrhea.

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I have had hemolytic anemia or bone marrow failure.

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I have not received a live vaccine within the last 4 weeks and do not plan to during or within 5 months after treatment.

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I have or had an autoimmune disease or immune deficiency.

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I have brain metastases that are untreated or getting worse.

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I have a history of specific lung conditions or signs of lung inflammation on a CT scan.

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I have heart problems or have had them in the past.

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I haven't taken any immune-weakening drugs in the last 2 weeks and don't plan to during the study.

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I have had a condition where my lymphocytes multiply unusually.

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I cannot confirm my eligibility for the trial due to lack of valid PIK3CA mutation test results.

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I haven't had cancer in the last 5 years, except for skin cancer.

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I have had a previous transplant of stem cells or an organ.

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I have a condition or had surgery that affects how my body absorbs food.

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I have had leptomeningeal disease.

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I have high cholesterol or triglycerides that aren't managed.

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I have active tuberculosis.

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I have Type 2 diabetes and am on treatment, or I have a history of Type 1 diabetes.

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I have been treated with an Akt inhibitor before.

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I have pain from my cancer that isn't relieved by treatment.

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I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.

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I frequently need procedures to remove excess fluid from my chest or abdomen.

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I have an active Hepatitis B or C infection.

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I have previously been treated with specific immune therapies.

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I cannot swallow pills or have a condition that affects how my body absorbs medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Active Control

Group I: Cohort 2: Giredestrant + PH FDC SC + PalbociclibExperimental Treatment3 Interventions

Group II: Cohort 2: Giredestrant + PH FDC SC + AbemaciclibExperimental Treatment3 Interventions

Group III: Cohort 1: Giredestrant + SamuraciclibExperimental Treatment2 Interventions

Group IV: Cohort 1: Giredestrant + RibociclibExperimental Treatment2 Interventions

Group V: Cohort 1: Giredestrant + IpatasertibExperimental Treatment2 Interventions

Group VI: Cohort 1: Giredestrant + InavolisibExperimental Treatment2 Interventions

Group VII: Cohort 1: Giredestrant + EverolimusExperimental Treatment2 Interventions

Group VIII: Cohort 1: Giredestrant + AtezolizumabExperimental Treatment2 Interventions

Group IX: Cohort 1: Giredestrant + Abemaciclib + AtezolizumabExperimental Treatment3 Interventions

Group X: Cohort 1: Giredestrant + AbemaciclibExperimental Treatment2 Interventions

Group XI: Cohort 2: Giredestrant + PH FDC SCActive Control2 Interventions

Group XII: Cohort 1: Giredestrant MonotherapyActive Control1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Inavolisib

2021

Completed Phase 2

~260

Palbociclib

2017

Completed Phase 3

~3880

Giredestrant

2019

Completed Phase 2

~300

Abemaciclib

2019

Completed Phase 2

~1890

Ipatasertib

2017

Completed Phase 3

~3630

Atezolizumab

2016

Completed Phase 3

~5860

Ribociclib

2018

Completed Phase 3

~2420

Everolimus

2010

Completed Phase 4

~1510

0 / 43Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for breast cancer include targeted therapies, antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). Targeted therapies, like trastuzumab, bind to the HER2 receptor on cancer cells, inhibiting their growth. ADCs, such as ado-trastuzumab emtansine, deliver cytotoxic drugs directly to cancer cells, reducing harm to normal cells. TKIs, like lapatinib, block enzymes that promote cancer cell proliferation. These treatments are important for breast cancer patients as they offer more precise and potentially more effective options with fewer side effects compared to traditional chemotherapy.

Human Epidermal Growth Factor Receptor 2-Targeting Approaches for Colorectal Cancer: Clinical Implications of Novel Treatments and Future Therapeutic Avenues.New drugs for breast cancer.Safety profile of new anticancer drugs.