Trastuzumab Deruxtecan + Durvalumab for Breast Cancer

(TRUDI Trial)

Recruiting at 2 trial locations

Overseen By Filipa Lynce, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Filipa Lynce, MD

Must not be taking: Steroids, Immunosuppressants, Hydroxychloroquine, others

Disqualifiers: Autoimmune disorders, Heart conditions, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 14

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to determine if it can safely and effectively treat inflammatory breast cancer with a specific marker called HER2. It involves two drugs: trastuzumab deruxtecan (a targeted therapy) and durvalumab (an immunotherapy), administered to participants before surgery. The trial divides participants into groups based on whether the cancer is HER2-positive or has low HER2 levels. Suitable candidates have been diagnosed with stage III inflammatory breast cancer within the last 6 months and have not yet received any treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you have used certain medications like potent inhibitors or inducers of specific enzymes (CYP3A4, CYP2C9, CYP2D6) or hydroxychloroquine shortly before starting the trial. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of trastuzumab deruxtecan and durvalumab has been studied for safety in treating certain breast cancers. Trastuzumab deruxtecan, often used for HER2-positive breast cancer, is generally well-tolerated. Some patients have experienced side effects like nausea and low blood cell counts, but these can be managed.

Durvalumab boosts the immune system's ability to fight cancer and has been studied for safety in various cancers. Common side effects include fatigue and cough.

This is a Phase 2 trial, indicating that earlier studies have demonstrated some safety. However, side effects can vary from person to person. Joining this trial helps researchers learn more about the safety and effectiveness of these treatments when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about trastuzumab deruxtecan combined with durvalumab for breast cancer because it offers a unique approach compared to standard treatments like chemotherapy, trastuzumab, and pertuzumab. Trastuzumab deruxtecan is an antibody-drug conjugate that specifically targets HER2 proteins on cancer cells, delivering chemotherapy directly to the tumor, which may enhance effectiveness and reduce side effects. Durvalumab, an immune checkpoint inhibitor, boosts the body's immune response against cancer cells. This combination may offer a more targeted and potentially more effective treatment, especially for patients with HER2-low or HER2-positive breast cancer, by both attacking the cancer directly and enhancing the immune system’s response.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will test the combination of trastuzumab deruxtecan and durvalumab for treating inflammatory breast cancer. Research has shown that trastuzumab deruxtecan effectively treats both HER2-positive and HER2-low breast cancer. In one study, patients with HER2-positive cancer achieved significantly better results compared to standard treatments. Specifically, for those with HER2-low breast cancer, the average time patients lived without disease progression was 13.2 months, surpassing the 8.1 months observed with regular chemotherapy. Durvalumab, when combined with other treatments, has been studied for its ability to enhance the immune system's fight against cancer. This trial tests these drugs together to determine if they can be even more effective in treating inflammatory breast cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I know my cancer's ER and PR status.

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

Must have a life expectancy of at least 12 weeks

Exclusion Criteria

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

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

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery

24 weeks

8 cycles (each cycle is 21 days)

Surgery

Surgery occurs no later than 6 weeks post 8 cycles of neoadjuvant therapy

Up to 6 weeks

Post-Surgery Treatment

Participants receive therapy per physician's choice and to reflect current standard of care

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Follow-up assessments every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Trastuzumab deruxtecan

Trial Overview 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.

How Is the Trial Designed?

Group I: HER2-Low Experimental Treatment 2 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 Positive Experimental Treatment 2 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.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Filipa Lynce, MD

Lead Sponsor

Trials

2

Recruited

140+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Industry Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Published Research Related to This Trial

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

In the DESTINY-Breast03 trial involving 524 patients with HER2-positive metastatic breast cancer, trastuzumab deruxtecan significantly improved median progression-free survival to 28.8 months compared to 6.8 months for trastuzumab emtansine, indicating its superior efficacy.

Trastuzumab deruxtecan also demonstrated a favorable safety profile, with similar rates of severe adverse events compared to trastuzumab emtansine, although it was associated with a higher incidence of interstitial lung disease (15% vs. 3%), suggesting careful monitoring is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Hurvitz, SA., Hegg, R., Chung, WP., et al.[2023]

Fam-trastuzumab deruxtecan-nxki (T-DXd) has been approved for treating HER2-low metastatic breast cancer, showing significant improvements in progression-free survival (PFS) and overall survival (OS) in a phase III trial with 557 patients.

The study demonstrated a 50% reduction in the risk of disease progression and a 36% reduction in the risk of death compared to standard chemotherapy, with a safety profile consistent with previous uses of T-DXd and no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. Narayan, P., Dilawari, A., Osgood, C., et al.[2023]

In the DESTINY-Breast01 trial with 184 patients, trastuzumab deruxtecan (T-DXd) showed a confirmed objective response rate of 62.0% and a median overall survival of 29.1 months, indicating its effectiveness in treating HER2-positive metastatic breast cancer after previous treatment with trastuzumab emtansine.

While T-DXd demonstrated sustained antitumor activity, it also had a notable safety profile, with 99.5% of patients experiencing drug-related adverse events, including a 15.8% incidence of interstitial lung disease/pneumonitis, highlighting the importance of monitoring for serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01). Saura, C., Modi, S., Krop, I., et al.[2023]

Trastuzumab deruxtecan (T-DXd) is a promising new antibody-drug conjugate that has been approved for treating HER2-positive metastatic breast cancer and gastric cancer, showing potential for use in other solid tumors as well.

T-DXd is expected to become the standard second-line treatment for HER2-positive metastatic breast cancer and may also benefit patients with hormone receptor-positive and triple-negative breast cancer that express low levels of HER2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. Perez, J., Garrigós, L., Gion, M., et al.[2022]

In a phase 2 study involving 184 patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a significant response rate of 60.9%, with a median response duration of 14.8 months.

While trastuzumab deruxtecan showed promising efficacy, it was associated with notable adverse effects, including interstitial lung disease in 13.6% of patients, highlighting the need for careful monitoring of pulmonary symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. Modi, S., Saura, C., Yamashita, T., et al.[2021]

In the phase 3 DESTINY-Breast02 trial involving 608 patients with HER2-positive metastatic breast cancer, trastuzumab deruxtecan significantly improved median progression-free survival to 17.8 months compared to 6.9 months for treatment of physician's choice, demonstrating its efficacy in a population with limited treatment options.

While trastuzumab deruxtecan had a higher incidence of treatment-emergent adverse events, including nausea and interstitial lung disease, it still showed a favorable benefit-risk profile, indicating its potential as a viable treatment option for patients resistant to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. André, F., Hee Park, Y., Kim, SB., et al.[2023]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41036093/

Efficacy of Trastuzumab Deruxtecan in HER2-Positive and ... In this real-world analysis, T-DXd demonstrated robust clinical activity in both HER2-positive and HER2-low MBC, consistent with the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12479221/

Efficacy of Trastuzumab Deruxtecan in HER2-Positive and ... In this retrospective study, we analyzed the real-world effectiveness of T-DXd in a cohort of patients with HER2-positive and HER2-low MBC, ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/761139Orig1s028.pdf

761139_Review Package - accessdata.fda.gov Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY ...

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-demonstrated-highly-statistically-significant-and-clinically-meaningful-improvement-in-invasive-disease-free-survival-vs-T-DM1-in-DESTINY-Breast05-Phase-III-trial-in-patients-with-high-risk-early-breast-cancer-following-neoadjuvant-therapy.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) ... This is the second positive Phase III trial of ENHERTU in the HER2-positive early breast cancer setting following positive results from the ...

5. enhertuhcp.com enhertuhcp.com/en/her2-low-her2-ultralow-breast/efficacy/her2-low

Efficacy in HR+/HER2-low mBC - Enhertu In patients with HR+/HER2-low (IHC 1+ or IHC 2+/ISH–) mBC. ENHERTU provided 13.2 months median PFS vs 8.1 months with chemotherapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03734029

NCT03734029 | Trastuzumab Deruxtecan (DS-8201a) ... This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice ( ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40947843/

Real-world safety and efficacy of trastuzumab deruxtecan ... Purpose: The efficacy of trastuzumab deruxtecan (T-DXd) has been demonstrated in large, phase III studies in HER2-positive (HER2+) and HER2-low ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04538742

NCT04538742 | A Phase 1b/2 Study of T-DXd ... This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents.