What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those similar to Dato-DXd and Durvalumab, have a range of side effects. Antibody-drug conjugates like trastuzumab deruxtecan can cause decreased neutrophil count, anemia, nausea, and interstitial lung disease. Immune checkpoint inhibitors such as pembrolizumab and durvalumab often lead to immune-related adverse events including fatigue, rash, diarrhea, and pneumonitis. Severe side effects may include colitis, hepatitis, endocrinopathies, and severe pneumonitis.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that are similar to Dato-DXd and Durvalumab. Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) approved for HER2-positive metastatic breast cancer. Another ADC, fam-trastuzumab deruxtecan (T-DXd), has shown efficacy in patients with HER2-positive breast cancer who have progressed on multiple prior therapies. For immune checkpoint inhibitors, Pembrolizumab, a PD-1 inhibitor, has been approved for PD-L1 positive triple-negative breast cancer in combination with chemotherapy. These approvals highlight the evolving landscape of targeted and immunotherapy treatments in breast cancer.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) Trastuzumab emtansine (T-DM1) combined with pertuzumab for HER2-positive metastatic breast cancer, which has shown efficacy in clinical trials. 2) Atezolizumab combined with nab-paclitaxel for triple-negative breast cancer, which has demonstrated prolonged progression-free survival in the IMpassion130 trial. These treatments offer different mechanisms of action and have shown promising results in clinical studies.

← Back to Search

Antitumor Antibiotic

Dato-DXd +/− Durvalumab vs Chemotherapy + Pembrolizumab for Triple-Negative 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

All participants must provide a FFPE metastatic or locally recurrent inoperable tumour sample

Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)

Must not have

Known HIV infection that is not well controlled

Severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, significant cardiac or psychological conditions

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomisation until progression per recist 1.1 as assessed by bicr, or death due to any cause (anticipated to be up to 33 months).

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests a new drug combination for advanced breast cancer patients whose cancer has returned or spread. It compares the new drugs to standard chemotherapy to see if they help patients live longer without their cancer getting worse. The new treatment aims to kill cancer cells directly and help the immune system fight the cancer. Lapatinib is a novel drug currently being tested in advanced breast cancer.

Who is the study for?

This trial is for adults with PD-L1 positive triple-negative breast cancer that's locally recurrent and inoperable or has spread (metastatic). They should not have had prior chemo or targeted therapy for their advanced disease, must have measurable disease per specific criteria, and proper organ function. Participants need to agree to use contraception if they can have children.

What is being tested?

The study compares the effectiveness of Dato-DXd alone or combined with Durvalumab against standard chemotherapy paired with Pembrolizumab. It's a Phase III trial where patients are randomly assigned to one of these three treatment groups to see which works best.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in various organs, infusion-related reactions, fatigue, blood disorders like anemia or clotting issues, potential liver problems and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

Select...

I can provide a tissue sample from my cancer that cannot be removed by surgery.

Select...

I am eligible for chemotherapy with paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin.

Select...

My triple-negative breast cancer is PD-L1 positive with a CPS of 10 or more.

Select...

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

Select...

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

Select...

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

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

Select...

My HIV infection is not well controlled.

Select...

I do not have severe illnesses, recent organ transplants, bleeding disorders, infections, or major heart or mental health issues.

Select...

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

Select...

I have a serious heart condition that is not under control.

Select...

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

Select...

I have been treated with drugs targeting topoisomerase I or TROP2.

Select...

I am not currently receiving any cancer treatments.

Select...

I am severely allergic to PD-1/PD-L1 inhibitors or Dato-DXd.

Select...

I have or had an autoimmune or inflammatory disorder.

Select...

I do not have cancer spread to my brain, spinal cord, or its coverings.

Select...

I have a serious eye condition affecting my cornea.

Select...

I do not have an infection needing IV drugs.

Select...

I have severe lung problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomisation until progression per recist 1.1 as assessed by bicr, or death due to any cause (anticipated to be up to 33 months).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomisation until progression per recist 1.1 as assessed by bicr, or death due to any cause (anticipated to be up to 33 months).

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomisation until progression per recist 1.1 as assessed by bicr, or death due to any cause (anticipated to be up to 33 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

Progression Free Survival (PFS)

Secondary study objectives

Clinical Benefit Rate (CBR) at 24 weeks

Duration of Response (DoR)

Immunogenicity of Dato-DXd in combination with durvalumab

+12 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

3Treatment groups

Experimental Treatment

Active Control

Group I: Dato-DXd + durvalumabExperimental Treatment2 Interventions

Arm 1: Dato-DXd + durvalumab

Group II: Dato-DXdExperimental Treatment1 Intervention

Arm 3: Dato-DXd

Group III: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumabActive Control5 Interventions

Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3750

0 / 19Eligibility 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 target cancer cells by combining a monoclonal antibody with a cytotoxic drug, ensuring that the chemotherapy is delivered directly to the cancer cells, thus sparing healthy cells. PD-L1 inhibitors such as Durvalumab block the PD-L1 protein on cancer cells, which helps the immune system recognize and attack the cancer. These mechanisms are significant for breast cancer patients as they offer more targeted and potentially more effective treatments with reduced side effects compared to conventional chemotherapy.

Pharmacokinetics of trastuzumab emtansine (T-DM1) as a single agent or in combination with pertuzumab in HER2-positive breast cancer patients with recurrent or locally advanced metastatic breast cancer.