Trastuzumab Deruxtecan + Durvalumab for Breast Cancer

(TRUDI Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Filipa Lynce, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Filipa Lynce, MD

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

Disqualifiers: Autoimmune disorders, Heart conditions, Infections, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Trastuzumab Deruxtecan + Durvalumab for breast cancer?

Research shows that Trastuzumab Deruxtecan (T-DXd) is effective in treating HER2-positive metastatic breast cancer, with studies like DESTINY-Breast03 demonstrating better survival outcomes compared to other treatments. Additionally, it has been approved for use in certain types of breast cancer, indicating its effectiveness. ^{1 2 3 4 5}

What safety information is available for Trastuzumab Deruxtecan and Durvalumab in humans?

Trastuzumab Deruxtecan (Enhertu) has been associated with some serious side effects, including interstitial lung disease (lung inflammation), which can be severe or life-threatening, and other common side effects like nausea, fatigue, and decreased appetite. It has a generally manageable safety profile, but careful monitoring is required, especially for lung-related issues. ^{3 4 5 6 7}

What makes the drug Trastuzumab Deruxtecan + Durvalumab unique for breast cancer treatment?

Trastuzumab Deruxtecan is a unique drug because it is an antibody-drug conjugate that targets HER2 (a protein that can promote the growth of cancer cells) and delivers a chemotherapy agent directly to the cancer cells, which can be effective even in HER2-low breast cancer. This combination with Durvalumab, an immune checkpoint inhibitor, is novel as it aims to enhance the immune system's ability to fight cancer, offering a new approach for patients with advanced breast cancer who have limited treatment options. ^{1 3 6 8 9}

Research Team

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Durvalumab (Monoclonal Antibodies)
• Trastuzumab deruxtecan (Antibody-drug conjugate)

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.

Participant Groups

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 Japan for the following indications:

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

Findings from Research

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-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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. England 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. [2023]

3. England 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). [2023]

4. England 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. [2023]

5. England 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. [2023]

6. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. [2022]