What is the mechanism of action of this treatment?

Common treatments for breast cancer, particularly those similar to Trastuzumab Deruxtecan (T-DXd), include antibody-drug conjugates (ADCs) and targeted therapies. ADCs like T-DXd target specific antigens such as HER2 on cancer cells and deliver a cytotoxic drug directly to these cells, enhancing treatment efficacy and minimizing damage to normal cells. This targeted approach is crucial for breast cancer patients as it improves outcomes and reduces systemic side effects. Other treatments, such as CDK inhibitors and endocrine therapies, disrupt cell cycle regulation and hormone signaling pathways, respectively, which are vital for the growth and proliferation of certain breast cancer subtypes.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, especially those targeting HER2 like Trastuzumab Deruxtecan (T-DXd), often have several side effects. T-DXd can cause decreased neutrophil count, anemia, nausea, and interstitial lung disease, which may present as cough, dyspnea, or fever. Other HER2-targeted therapies, such as Trastuzumab and Ado-trastuzumab emtansine (T-DM1), can lead to cardiac issues, fatigue, and liver function abnormalities. Chemotherapy regimens, often used in combination, may result in hair loss, nausea, fatigue, and increased risk of infections. Hormone therapies, like tamoxifen and aromatase inhibitors, can cause hot flashes, bone density loss, and cardiovascular risks.

What prior FDA approvals exist?

The FDA has approved several antibody-drug conjugates (ADCs) for the treatment of HER2-positive breast cancer. Trastuzumab emtansine (T-DM1) is approved for patients who have progressed after trastuzumab and a taxane, including those with treated, stable brain metastases. Fam-trastuzumab deruxtecan (T-DXd) is another ADC that has shown efficacy in patients with HER2-positive metastatic breast cancer, including those with brain metastases. Both drugs combine the targeting ability of trastuzumab with cytotoxic agents to kill cancer cells. Notable toxic effects include interstitial lung disease for T-DXd and decreased neutrophil count for both drugs.

What other types of research exist?

Promising alternatives to T-DXd for breast cancer patients include the tucatinib-trastuzumab-capecitabine regimen, which has shown efficacy in treating leptomeningeal metastasis in HER2-positive breast cancer. Additionally, trastuzumab emtansine (T-DM1) has demonstrated effectiveness in patients with brain metastases and HER2-positive breast cancer. These alternatives offer targeted treatment options with proven efficacy in clinical trials.

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Hormone Therapy

T-DXd Combinations for Breast Cancer (DB-08 Trial)

Phase 1

Waitlist Available

Led By Komal Jhaveri, MD, FACP

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Patients must be at least 18 years of age

ECOG Performance Status of 0 or 1

Must not have

History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to follow-up period, approximately 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing T-DXd with other treatments in patients with a specific type of advanced breast cancer that has low levels of HER2. The study aims to find the best dose and see how well the treatment works and how safe it is. T-DXd is a new treatment that has shown promising outcomes in various studies for advanced breast cancers with different levels of HER2.

Who is the study for?

This trial is for adults with HER2-low advanced or metastatic breast cancer. Eligible patients must have received certain prior treatments depending on their hormone receptor status, and should not have significant lung disease, uncontrolled infections or illnesses, cardiovascular issues, a history of specific lung conditions, primary immunodeficiency, spinal cord compression or active brain metastases.

What is being tested?

The DESTINY-Breast 08 study tests the combination of T-DXd (Trastuzumab deruxtecan) with other therapies like Fulvestrant, Durvalumab, Capivasertib, Anastrozole, Paclitaxel and Capecitabine in treating HER2-low advanced/metastatic breast cancer to evaluate safety and early anti-tumor effects.

What are the potential side effects?

Potential side effects may include reactions related to the immune system's response to treatment components such as inflammation in various organs. Specific side effect profiles will depend on the drug combinations used but can range from mild symptoms like fatigue to more serious conditions.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My breast cancer is HER2-low, hormone receptor positive, and not responsive to estrogen or progesterone.

Exclusion Criteria

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

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I have or had lung inflammation treated with steroids, or it can't be ruled out by scans.

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I have been treated with a specific drug that targets cancer cells.

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I do not have any uncontrolled illnesses.

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My cancer has spread to my brain or spinal cord.

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I have serious lung-related health issues.

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I do not have an infection needing IV drugs.

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I have serious heart problems that are not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to follow-up period, approximately 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to follow-up period, approximately 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to follow-up period, approximately 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Occurrence of adverse events (AEs)- Part 1

Occurrence of adverse events (AEs)- Part 2

Occurrence of serious adverse events (SAEs)- Part 1

+1 more

Secondary study objectives

Duration of Response (DoR)- Part 2

Immunogenicity of durvalumab

Immunogenicity of trastuzumab deruxtecan

+5 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: Module 5: T-DXd + fulvestrantExperimental Treatment2 Interventions

T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use

Group II: Module 4: T-DXd + anastrozoleExperimental Treatment2 Interventions

T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral

Group III: Module 3: T-DXd + capivasertibExperimental Treatment2 Interventions

T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use

Group IV: Module 2: T-DXd + durvalumab + paclitaxelExperimental Treatment3 Interventions

T-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use

Group V: Module 1: T-DXd + capecitabineExperimental Treatment2 Interventions

T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fulvestrant

2011

Completed Phase 3

~3510

Trastuzumab deruxtecan

2021

Completed Phase 2

~730

Anastrozole

2016

Completed Phase 4

~5550

Durvalumab

2017

Completed Phase 2

~3750

Paclitaxel

2011

Completed Phase 4

~5370

Capecitabine

2013

Completed Phase 3

~3960

Capivasertib

2021

Completed Phase 1

~130

0 / 10Eligibility 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, particularly those similar to Trastuzumab Deruxtecan (T-DXd), include antibody-drug conjugates (ADCs) and targeted therapies. ADCs like T-DXd target specific antigens such as HER2 on cancer cells and deliver a cytotoxic drug directly to these cells, enhancing treatment efficacy and minimizing damage to normal cells. This targeted approach is crucial for breast cancer patients as it improves outcomes and reduces systemic side effects. Other treatments, such as CDK inhibitors and endocrine therapies, disrupt cell cycle regulation and hormone signaling pathways, respectively, which are vital for the growth and proliferation of certain breast cancer subtypes.

SABCS 2020: update on triple-negative and metastatic HER2-positive breast cancer.CDK inhibitors as potential breast cancer therapeutics: new evidence for enhanced efficacy in ER+ disease.New concepts in breast cancer therapy.