What is the mechanism of action of this treatment?

Antibody-Drug Conjugates (ADCs) like Dato-DXd work by combining a monoclonal antibody specific to cancer cell antigens with a cytotoxic drug. The antibody targets and binds to cancer cells, delivering the cytotoxic drug directly to the tumor, which minimizes damage to healthy cells. This targeted approach enhances the efficacy of the treatment while reducing systemic toxicity. For breast cancer patients, especially those with triple-negative breast cancer (TNBC), this mechanism is crucial as it offers a more effective and potentially less harmful treatment option compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly Antibody-Drug Conjugates (ADCs) like Dato-DXd, often include side effects such as decreased neutrophil count, anemia, nausea, and interstitial lung disease. Other side effects may include fatigue, diarrhea, and neuropathy. These treatments target cancer cells specifically, but they can still affect healthy cells, leading to these adverse effects. Monitoring and managing these side effects are crucial for maintaining the patient's quality of life during treatment.

What prior FDA approvals exist?

The FDA has approved several antibody-drug conjugates (ADCs) for the treatment of breast cancer. Notably, trastuzumab emtansine (T-DM1) is an ADC used for HER2-positive metastatic breast cancer, combining the HER2-targeting properties of trastuzumab with the cytotoxic agent DM1. Another ADC, fam-trastuzumab deruxtecan (T-DXd), has been approved for HER2-positive breast cancer patients who have previously received trastuzumab and a taxane. These treatments work by delivering cytotoxic drugs directly to cancer cells, thereby minimizing damage to normal cells.

What other types of research exist?

Promising novel alternatives to Dato-DXd for breast cancer patients include: 1) Trastuzumab Deruxtecan (Enhertu), another antibody-drug conjugate targeting HER2-positive breast cancer. 2) Sacituzumab Govitecan (Trodelvy), an antibody-drug conjugate targeting Trop-2 for triple-negative breast cancer. 3) Pembrolizumab (Keytruda), an immune checkpoint inhibitor for PD-L1 positive breast cancer. 4) Alpelisib (Piqray), a PI3K inhibitor for HR-positive, HER2-negative breast cancer with PIK3CA mutations.

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Antibody-drug conjugate

Dato-DXd +/− Durvalumab for Breast Cancer

Phase 3

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Participant must be ≥ 18 years at the time of screening.

Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.

Must not have

Stage IV (metastatic) TNBC.

History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up randomization to date of death, due to any cause, up to 87 months from first subject in

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing a new treatment for patients with a specific type of breast cancer who still have cancer after surgery and initial treatments. The treatment uses a drug called Dato-DXd, which targets and kills cancer cells, and may also include durvalumab, which helps the immune system fight cancer. The goal is to see if this new treatment works better than current options.

Who is the study for?

Adults over 18 with stage I-III triple-negative breast cancer who didn't have a complete response after neoadjuvant therapy. They must have finished at least 6 cycles of specific chemotherapy, had surgery to remove the disease, and can't be in relapse. Participants need good heart function and overall health but can't join if they've had certain severe diseases, other cancers within 5 years, or known genetic mutations related to breast cancer.

What is being tested?

The study is testing Dato-DXd alone or combined with Durvalumab against standard treatments chosen by the investigator for patients with triple-negative breast cancer post-surgery. It's an open-label trial where everyone knows which treatment they're getting, and it involves multiple international centers.

What are the potential side effects?

Possible side effects include immune system reactions that may affect organs, infusion-related symptoms like fever or chills, fatigue, gastrointestinal issues such as diarrhea or nausea, blood disorders leading to increased risk of infections or bleeding problems. Specific side effects depend on each drug's profile.

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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My breast cancer is triple-negative, confirmed by a biopsy.

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I still have cancer in my breast or lymph nodes after initial treatment.

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I've completed 6+ cycles of specific chemo before surgery for my cancer.

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My cancer has not returned or spread after treatment.

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I had surgery to remove all visible cancer from my breast and lymph nodes.

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I can provide a tissue sample from my cancer surgery for analysis.

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I have not received any additional treatment after my primary cancer treatment.

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I do not have a known BRCA1 or BRCA2 gene mutation.

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My organs and bone marrow are working well.

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I am 18 years old or older.

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My breast cancer is triple-negative, confirmed by a biopsy.

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I still have cancer in my breast or lymph nodes after initial treatment.

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I've completed 6 cycles of specific chemotherapy for my cancer.

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My cancer has not returned or spread after treatment.

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I had surgery to remove all visible cancer from my breast and lymph nodes.

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I can provide a tissue sample from my surgery for analysis.

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I have not received any additional treatment after my primary cancer treatment.

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I do not have a known BRCA1 or BRCA2 gene mutation.

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My organs and bone marrow are working well.

Exclusion Criteria

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

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My breast cancer has spread to other parts of my body.

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I have had breast cancer before or it came back after initial treatment.

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I do not have severe illnesses, recent organ transplants, bleeding issues, infections, or chronic diarrhea.

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I have or had an autoimmune or inflammatory disorder.

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I have a serious eye condition affecting my cornea.

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I do not have active or uncontrolled hepatitis B or C.

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I do not have an active tuberculosis infection.

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I do not have any major heart problems.

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I have or had lung inflammation treated with steroids, or it's suspected but not confirmed by scans.

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I have severe lung problems due to another lung condition.

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I have an active liver disease.

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I have moderate to severe nerve damage in my hands or feet.

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I have been treated with a PD-1/PD-L1 inhibitor, but not pembrolizumab.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ randomization to date of death, due to any cause, up to 87 months from first subject in

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~randomization to date of death, due to any cause, up to 87 months from first subject in

This trial's timeline: 3 weeks for screening, Varies for treatment, and randomization to date of death, due to any cause, up to 87 months from first subject in for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT

Secondary study objectives

DDFS for Dato-DXd + durvalumab vs Dato-DXd

DDFS for Dato-DXd vs ICT

Distant disease-free survival (DDFS) for Dato-DXd + durvalumab vs ICT

+10 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Dato-DXd in combination with DurvalumabExperimental Treatment2 Interventions

Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles

Group II: Dato-DXdExperimental Treatment1 Intervention

Arm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles

Group III: Investigators Choice TherapyActive Control2 Interventions

Arm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles Pembrolizumab* (200 mg IV on Day 1, Q3W) for 9 cycles Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab* (200 mg IV on Day 1, Q3W) for 9 cycles * Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3750

0 / 33Eligibility 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

Antibody-Drug Conjugates (ADCs) like Dato-DXd work by combining a monoclonal antibody specific to cancer cell antigens with a cytotoxic drug. The antibody targets and binds to cancer cells, delivering the cytotoxic drug directly to the tumor, which minimizes damage to healthy cells. This targeted approach enhances the efficacy of the treatment while reducing systemic toxicity. For breast cancer patients, especially those with triple-negative breast cancer (TNBC), this mechanism is crucial as it offers a more effective and potentially less harmful treatment option compared to traditional chemotherapy.

Antibody-drug conjugates as novel anti-cancer chemotherapeutics.Indications and limitations of third-generation aromatase inhibitors.Endocrine therapy for early breast cancer.