What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving antibody-drug conjugates (ADCs) like trastuzumab deruxtecan and immune checkpoint inhibitors like durvalumab, have specific side effects. Trastuzumab deruxtecan can cause decreased neutrophil count, anemia, nausea, and interstitial lung disease, which may present as cough, dyspnea, and fever. Durvalumab, an immune checkpoint inhibitor, may lead to immune-related adverse events such as fatigue, skin rash, diarrhea, and potential inflammation of organs like the lungs (pneumonitis) and liver (hepatitis). These side effects necessitate careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that are similar to trastuzumab deruxtecan and durvalumab. Trastuzumab deruxtecan (an antibody-drug conjugate targeting HER2) is approved for patients with unresectable or metastatic HER2-positive breast cancer who have received prior anti-HER2-based regimens. Another similar treatment is neratinib, approved in combination with capecitabine for advanced HER2-positive breast cancer after two or more prior anti-HER2-based regimens. While durvalumab (an immune checkpoint inhibitor targeting PD-L1) is not specifically mentioned for breast cancer, pembrolizumab, another PD-1/PD-L1 inhibitor, is approved for PD-L1-positive endometrial cancer and has shown activity in other cancers, suggesting potential applicability in breast cancer.

What other types of research exist?

Promising alternatives to Trastuzumab deruxtecan and Durvalumab for breast cancer patients include: <ol> <li>Tucatinib-Trastuzumab-Capecitabine regimen: This combination has shown efficacy in treating HER2-positive breast cancer with brain metastases.</li> <li></li> </ol> Trastuzumab Emtansine (T-DM1): Effective for patients who progress after trastuzumab and a taxane, with reported CNS objective response rates between 20-44%. 3. Sacituzumab Govitecan: Demonstrated efficacy in hormone receptor-positive/HER2-negative advanced breast cancer in the TROPiCS-02 study. 4. Pembrolizumab: An immune checkpoint inhibitor targeting PD-1, showing activity in various cancers, including breast cancer.

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Monoclonal Antibodies

Trastuzumab Deruxtecan + Durvalumab for Breast Cancer (TRUDI Trial)

Phase 2

Recruiting

Research Sponsored by Filipa Lynce, MD

Eligibility Criteria Checklist

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

Must have

Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with durvalumab and 4 months after the last dose of study treatment

Body weight >30 kg

Must not have

Active infection including tuberculosis, hepatitis B or hepatitis C virus

History of leptomeningeal carcinomatosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up disease assessed every 6 weeks by chest xray (+/- 1 week) until completion of 8 cycles of neo-adjuvant therapy (one cycle=21 days); follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, trastuzumab deruxtecan and durvalumab, for treating stage III inflammatory breast cancer that has a specific protein called HER2. The study focuses on patients who have not received previous treatment for this type of breast cancer. Trastuzumab deruxtecan targets and kills cancer cells, while durvalumab helps the immune system attack the cancer. The goal is to see if this combination is safe and effective.

Who is the study for?

This trial is for adults with stage III inflammatory breast cancer that expresses HER2, who haven't had prior treatment for this diagnosis. They must be in good health overall, have a life expectancy of at least 12 weeks, weigh over 30 kg, and agree to biopsies and contraception methods if applicable. Exclusions include previous severe reactions to the drugs being tested or similar medications, recent major surgeries or heart issues, active infections like TB or hepatitis B/C, HIV positivity, certain other medical conditions or treatments.

What is being tested?

The TRUDI trial is testing the combination of two drugs: Trastuzumab deruxtecan and Durvalumab. It aims to determine their safety and effectiveness in treating HER2-positive inflammatory breast cancer. Participants will receive both medications as part of their treatment regimen.

What are the potential side effects?

Potential side effects may include allergic reactions to medication components; fatigue; nausea; changes in blood counts leading to increased infection risk; potential heart problems such as reduced ejection fraction; lung issues like inflammation (pneumonitis); liver function changes; and diarrhea.

Eligibility Criteria

Inclusion Criteria

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

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I agree to use birth control during and for 4 months after my treatment.

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I weigh more than 30 kilograms.

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I understand the study requirements and agree to participate.

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I have not received any treatment for my condition.

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My organ and bone marrow functions are normal.

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I am fully active or able to carry out light work.

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I have been diagnosed with invasive breast cancer.

Exclusion Criteria

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

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I do not have an active infection like TB, hepatitis B, or hepatitis C.

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I have had cancer spread to the lining of my brain and spinal cord.

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I do not have any serious ongoing illnesses that could worsen my condition or affect my participation.

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I have had treatments like chemotherapy for my inflammatory breast cancer.

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I have not had major surgery in the last 4 weeks or have fully recovered from it.

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I have had radiotherapy or surgery for my inflammatory breast cancer, but not just a biopsy.

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I am allergic to durvalumab, trastuzumab deruxtecan, or similar medications.

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I do not have serious lung conditions or autoimmune diseases affecting my lungs.

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My heart's pumping ability is within the normal range.

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I have or had an autoimmune or inflammatory disorder.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ disease assessed every 6 weeks by chest xray (+/- 1 week) until 8 cycles of neo-adjuvant therapy (one cycle=21 days); follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~disease assessed every 6 weeks by chest xray (+/- 1 week) until 8 cycles of neo-adjuvant therapy (one cycle=21 days); follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and disease assessed every 6 weeks by chest xray (+/- 1 week) until 8 cycles of neo-adjuvant therapy (one cycle=21 days); follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Pathological complete response (pCR) Rate

Secondary study objectives

Distant progression or distant disease-free survival (DP/DDFS)

Event Free Survival (EFS)

Residual Cancer Burden (RCB) Response

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: HER2-LowExperimental Treatment2 Interventions

Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2) * HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.

Group II: HER2 PositiveExperimental Treatment2 Interventions

Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2). * HER2-positive determined locally by the current ASCO/CAP guidelines * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery. (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab deruxtecan

2021

Completed Phase 2

~800

Durvalumab

2017

Completed Phase 4

~3880

0 / 18Eligibility 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 trastuzumab deruxtecan target the HER2 protein on cancer cells, delivering cytotoxic agents directly to the tumor and minimizing damage to normal cells. Immune checkpoint inhibitors like durvalumab target PD-L1, a protein that helps cancer cells evade the immune system, thereby enhancing the body's immune response against the tumor. These targeted therapies are crucial for breast cancer patients as they offer effective treatment options with potentially fewer side effects compared to traditional chemotherapy.

Evaluating human epidermal growth factor receptor 2 roles in the efficacy of Tamoxifen treatment in breast cancer, a systematic review.