What side effects are associated with this type of intervention?

Antibody-Drug Conjugates (ADCs) like Dato-DXd, which target HER2, are commonly used in breast cancer treatment. These treatments are associated with a range of side effects. Common adverse events include decreased neutrophil count, anemia, and nausea. Specific ADCs such as fam-trastuzumab deruxtecan have been linked to interstitial lung disease in a significant number of patients, with some cases being severe. Hair loss is also a variable side effect, depending on the specific ADC and its drug-to-antibody ratio. Other side effects can include fatigue, diarrhea, and rash, which are generally manageable.

What prior FDA approvals exist?

The FDA has approved several antibody-drug conjugates (ADCs) for the treatment of HER2-positive breast cancer. Fam-trastuzumab deruxtecan (T-DXd) is approved for patients with HER2-positive metastatic breast cancer who have progressed on prior treatments, showing significant efficacy in clinical trials. Another ADC, ado-trastuzumab emtansine (T-DM1), is approved for patients who have previously been treated with trastuzumab and a taxane. Both T-DXd and T-DM1 have demonstrated improved progression-free survival and overall survival in clinical studies, making them important options in the treatment landscape for HER2-positive breast cancer.

What other types of research exist?

Promising novel alternatives to Dato-DXd for breast cancer patients include Trastuzumab Deruxtecan (Enhertu), which has shown significant efficacy in HER2-positive metastatic breast cancer. Another option is Trastuzumab Emtansine (T-DM1), which has been effective in patients with previously treated HER2-positive advanced breast cancer. Additionally, PF-06804103, a new generation HER2 ADC, has demonstrated promising preclinical efficacy and may be a viable option in the near future.

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Anti-metabolites

Dato-DXd for Triple-negative Breast Cancer

Phase 3

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Negative for HER2 with 0 or 1+ intensity on IHC or 2+ intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guideline

At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and is suitable for accurate repeated measurements.

Must not have

Known active tuberculosis infection

History of any lymphoproliferative disorder

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomisation until progression per recist 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 26 months)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new drug called Dato-DXd to see if it works better than current treatments for patients with a specific type of breast cancer that has come back or spread and cannot be treated with certain common therapies. The drug aims to target and kill cancer cells more effectively.

Who is the study for?

This trial is for adults with triple-negative breast cancer that's locally recurrent and inoperable or has spread (metastatic), who haven't had chemotherapy for this condition, and can't use PD-1/PD-L1 inhibitor therapy. Participants need at least one measurable tumor lesion, good physical status (ECOG PS 0 or 1), adequate organ function, a life expectancy of over 12 weeks, and must not be pregnant or breastfeeding.

What is being tested?

The study compares Dato-DXd to standard chemotherapies like Paclitaxel and Nab-paclitaxel in patients with advanced triple-negative breast cancer. It's an open-label Phase III trial where participants are randomly assigned to either the test drug group or the control group receiving investigator's choice of chemotherapy.

What are the potential side effects?

Potential side effects include reactions related to infusion treatments, fatigue, hair loss (alopecia), digestive issues such as nausea and diarrhea, blood disorders like low white cell count which increases infection risk. Specific side effects from Dato-DXd may also occur.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is HER2 negative according to specific testing guidelines.

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I have a tumor that can be measured and has not been treated with radiation.

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I haven't had chemotherapy or targeted therapy for my advanced breast cancer.

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I haven't had chemotherapy or other cancer treatments for advanced breast cancer.

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My triple-negative breast cancer is inoperable or has spread and cannot be cured.

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I am 18 years old or older.

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My breast cancer is PD-L1 negative or has returned after PD-1/PD-L1 treatment.

Exclusion Criteria

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

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I have an active tuberculosis infection.

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I have had a condition where my lymphocytes grow abnormally.

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I have a history of cancer.

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I do not have significant heart issues, lung problems, or severe eye diseases.

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I haven't had certain cancer treatments, major surgery, or live vaccines recently.

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I still have side effects from cancer treatment, except for hair loss, that haven't improved.

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My HIV infection is not well controlled.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomisation until progression per recist 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 26 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomisation until progression per recist 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 26 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomisation until progression per recist 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 26 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

Overall Survival (OS)

Progression Free Survival (PFS)

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DoR)

Immunogenicity of Dato-DXd

+11 more

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Dato-DXdExperimental Treatment1 Intervention

Arm 1: Dato-DXd

Group II: Investigator's Choice of Chemotherapy (ICC)Active Control5 Interventions

Arm 2: If no prior taxane, or prior taxane in the (neo)adjuvant setting and DFI \> 12 months, paclitaxel or nab-paclitaxel If prior taxane and DFI ≤ 12 months: capecitabine, carboplatin, or eribulin.

0 / 15Eligibility 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 an antibody that targets a specific cancer cell marker (such as HER2) with a cytotoxic drug, allowing for targeted delivery directly to cancer cells. This targeted approach enhances treatment efficacy and reduces side effects compared to traditional chemotherapy, which affects both cancerous and healthy cells. Other treatments include hormone therapy, which blocks hormones that promote cancer growth, and standard chemotherapy, which kills rapidly dividing cells. Understanding these mechanisms is essential for selecting the most effective and least harmful treatment options for breast cancer patients.

Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin).