Dato-DXd +/− Durvalumab for Breast Cancer

Recruiting at 238 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, PD-1/PD-L1 inhibitors

Disqualifiers: Metastatic TNBC, Autoimmune disorders, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: 24-27 weeks

1174 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for patients with a specific type of breast cancer who still have cancer after surgery and initial treatments. The treatment uses a drug called Dato-DXd, which targets and kills cancer cells, and may also include durvalumab, which helps the immune system fight cancer. The goal is to see if this new treatment works better than current options.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before randomization.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have used immunosuppressive medication within 14 days before joining the trial.

What safety data is available for Dato-DXd and Durvalumab in breast cancer treatment?

The TROPION-Breast01 study is evaluating the safety of Datopotamab deruxtecan (Dato-DXd) compared to standard chemotherapy in patients with HR+/HER2- breast cancer. While specific safety data for Dato-DXd in combination with Durvalumab is not detailed in the provided research, Dato-DXd is an antibody-drug conjugate with a TROP2-directed monoclonal antibody linked to a topoisomerase I inhibitor. Safety profiles of similar drugs, like trastuzumab deruxtecan, indicate manageable adverse events such as low-grade hematologic and gastrointestinal issues, with interstitial lung disease/pneumonitis being a severe but observed risk. Further specific safety data for the combination with Durvalumab would likely be available from ongoing or future clinical trials. ^{1 2 3 4 5}

What is known about the safety of Dato-DXd and Durvalumab for breast cancer treatment?

Dato-DXd, an antibody-drug conjugate, is being studied for safety in breast cancer treatment, with common side effects including low-grade blood and stomach issues. Durvalumab, an immune therapy, has been used in various cancer treatments and is generally considered safe, but specific safety data for its combination with Dato-DXd in breast cancer is still being evaluated. ^{1 2 3 4 5}

Is the drug Dato-DXd a promising treatment for breast cancer?

The information provided does not directly address Dato-DXd, so we cannot determine if it is a promising treatment for breast cancer based on this data. ^{6 7 8 9 10}

What makes the drug Dato-DXd unique for breast cancer treatment?

Dato-DXd is unique because it is an antibody-drug conjugate, which means it combines an antibody that targets cancer cells with a chemotherapy drug, allowing for more precise delivery of the treatment directly to the cancer cells, potentially reducing side effects compared to traditional chemotherapy. ^{6 7 8 9 10}

What data supports the idea that Dato-DXd +/− Durvalumab for Breast Cancer is an effective treatment?

The available research shows that Dato-DXd is being tested in a phase 3 study called TROPION-Breast01, which compares its effectiveness to standard chemotherapy in patients with a specific type of breast cancer that is hard to treat. This study focuses on patients whose cancer has not responded to other treatments. Although the results are not detailed here, the fact that Dato-DXd is being compared to standard treatments in a large study suggests it has potential as an effective option. Additionally, another study, TROPION-Breast02, is testing Dato-DXd in a different type of breast cancer, further indicating its potential effectiveness. ^{1 3 11 12 13}

What data supports the effectiveness of the drug Dato-DXd for breast cancer?

Research shows that Dato-DXd, an antibody-drug conjugate, is being tested in clinical trials for its effectiveness in treating different types of breast cancer, including HR+/HER2- and triple-negative breast cancer. These trials aim to compare Dato-DXd with standard chemotherapy, suggesting it could be a promising option for patients with limited treatment choices. ^{1 3 11 12 13}

Research Team

Aditya Bardia, MD, MPH

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults over 18 with stage I-III triple-negative breast cancer who didn't have a complete response after neoadjuvant therapy. They must have finished at least 6 cycles of specific chemotherapy, had surgery to remove the disease, and can't be in relapse. Participants need good heart function and overall health but can't join if they've had certain severe diseases, other cancers within 5 years, or known genetic mutations related to breast cancer.

Inclusion Criteria

I have not received any additional treatment after my primary cancer treatment.

I can provide a tissue sample from my surgery for analysis.

I have not received any additional treatment after my primary cancer treatment.

Exclusion Criteria

Participants with a known severe hypersensitivity to Dato-DXd or any of the excipients of these products including but not limited to polysorbate 80 or other monoclonal antibodies.

I do not have an active tuberculosis infection.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dato-DXd with or without durvalumab or Investigator's Choice Therapy for 8-9 cycles

24-27 weeks

Every 3 weeks for 8-9 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

57 months

Long-term follow-up

Participants are monitored for overall survival and disease-free survival

Up to 87 months

Treatment Details

Interventions

• Capecitabine
• Dato-DXd
• Durvalumab
• Pembrolizumab

Trial Overview The study is testing Dato-DXd alone or combined with Durvalumab against standard treatments chosen by the investigator for patients with triple-negative breast cancer post-surgery. It's an open-label trial where everyone knows which treatment they're getting, and it involves multiple international centers.

Participant Groups

Group I: Dato-DXd in combination with Durvalumab Experimental Treatment 2 Interventions

Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles

Group II: Dato-DXd Experimental Treatment 1 Intervention

Arm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles

Group III: Investigators Choice Therapy Active Control 2 Interventions

Arm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles Pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles \* Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3.

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

SWOG Clinical Trials Partnership

Collaborator

Trials

1

Recruited

1,200+

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

SWOG Clinical Trials Partnerships

Collaborator

Trials

1

Recruited

1,200+

Findings from Research

Trastuzumab deruxtecan (T-DXd) has shown superior efficacy compared to capecitabine-based chemotherapy and T-DM1 in patients with metastatic HER2-positive breast cancer, based on the latest phase III data from the DESTINY-Breast02 and DESTINY-Breast03 trials.

T-DXd may also be effective as a neoadjuvant treatment for HER2-low breast cancer, suggesting its potential for broader applications in HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd Keeps Shining in Breast Cancer. [2023]

The phase III TROPION-Breast02 trial is investigating the efficacy and safety of the antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) in approximately 600 patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who have not received prior treatment.

Dato-DXd is designed to target TROP2 and deliver a topoisomerase I inhibitor directly to cancer cells, and the trial will compare its effectiveness against standard chemotherapy options, focusing on progression-free survival and overall survival as primary outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Dent, RA., Cescon, DW., Bachelot, T., et al.[2023]

Trastuzumab deruxtecan (T-DXd) is effective for breast cancer patients with low ERBB2 positivity (IHC scores of 1+ or 2+), but current standard assays show poor accuracy in distinguishing between low scores (0 and 1+), which could misassign patients for treatment.

In a study involving 18 pathologists assessing 170 breast cancer biopsies, there was only 26% concordance in scoring between 0 and 1+, indicating significant variability in ERBB2 IHC scoring that may impact patient eligibility for T-DXd.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. Fernandez, AI., Liu, M., Bellizzi, A., et al.[2023]

Datopotamab deruxtecan (Dato-DXd) is a promising new treatment for patients with metastatic HR+/HER2- breast cancer, particularly for those who have limited options after endocrine therapy and chemotherapy.

The ongoing phase III TROPION-Breast01 study is comparing the efficacy and safety of Dato-DXd against standard chemotherapy in patients who have already received one or two lines of systemic treatment, aiming to improve outcomes in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Bardia, A., Jhaveri, K., Kalinsky, K., et al.[2023]

In a real-world study of 143 patients with HER2+ metastatic breast cancer, trastuzumab deruxtecan (T-DXd) demonstrated a high overall response rate of 68% and a median progression-free survival of 16 months, confirming its efficacy in routine clinical practice.

The safety profile of T-DXd was consistent with previous studies, with 59% of patients experiencing any-grade toxicity, primarily nausea and neutropenia, but no new safety concerns were identified, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. Botticelli, A., Caputo, R., Scagnoli, S., et al.[2023]

Trastuzumab deruxtecan (T-DXd) was evaluated for safety in 1457 patients across 8 clinical trials, revealing that gastrointestinal disorders and blood-related issues were the most common adverse events, with neutropenia being the most severe (21.4% incidence).

The study highlighted significant concerns regarding interstitial lung disease (10.9% incidence) and decreased left ventricular ejection fraction (1.2% incidence), suggesting that while T-DXd is generally well tolerated, these specific side effects require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. Guo, Z., Ding, Y., Wang, M., et al.[2023]

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that effectively targets HER2-positive unresectable/metastatic breast cancer, showing a generally manageable safety profile with common low-grade side effects like nausea and neutropenia, but also carries risks of severe interstitial lung disease (ILD)/pneumonitis.

Effective management strategies for T-DXd-related adverse events, particularly proactive measures for nausea and ILD/pneumonitis, are crucial for maximizing treatment benefits and minimizing the risk of treatment discontinuation or dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. Rugo, HS., Bianchini, G., Cortes, J., et al.[2022]

Trastuzumab deruxtecan (T-DXd) has shown significant antitumor activity in patients with HER2-positive advanced gastric cancer (AGC) who have previously undergone at least two therapies, leading to its approval in Japan and by the US FDA.

The treatment resulted in a higher objective response rate and longer overall survival compared to previous therapies, with an acceptable safety profile, indicating its potential as an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. Mishima, S., Shitara, K.[2022]

In a large multinational trial (P024) involving postmenopausal women with hormone receptor-positive (HR+) breast cancer, neoadjuvant letrozole showed a significantly higher overall response rate (55%) compared to tamoxifen (36%), leading to more patients being eligible for breast-conserving surgery.

Letrozole was also more effective in reducing tumor proliferation and showed superior efficacy in both estrogen receptor-positive tumors and HER2+ subgroups, indicating its potential as a safer and more effective treatment option for HR+ locally advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole in the neoadjuvant setting: the P024 trial. Ellis, MJ., Ma, C.[2021]

Tamoxifen has been a groundbreaking treatment for breast cancer, but raloxifene offers a safer alternative with a lower risk of endometrial cancer and is being studied for breast cancer prevention.

Aromatase inhibitors (AIs) have shown greater efficacy than tamoxifen for both first-line and second-line therapies, and the pure antiestrogen fulvestrant is equally effective, highlighting the importance of these therapies in managing breast cancer, especially in cases resistant to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen receptors as therapeutic targets in breast cancer. Ariazi, EA., Ariazi, JL., Cordera, F., et al.[2018]

Fulvestrant 500 mg significantly improves the clinical benefit rate (CBR) in postmenopausal women with hormone receptor-positive advanced breast cancer compared to other endocrine therapies, based on a meta-analysis of six randomized controlled trials involving 1588 patients.

The analysis showed that fulvestrant 500 mg was particularly effective as a first-line treatment, with a notable odds ratio of 1.33 indicating a higher proportion of patients achieving a complete or partial response or stable disease for at least 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer. Robertson, JFR., Jiang, Z., Di Leo, A., et al.[2020]

In a study involving 1,354 women with advanced breast cancer, tamoxifen (20 mg/d) was found to be significantly more effective than droloxifene (40 mg/d) in delaying disease progression and achieving tumor response, with a hazard ratio of 1.287 favoring tamoxifen.

The objective response rate was 28.6% for tamoxifen compared to 22.4% for droloxifene, leading to the conclusion that droloxifene was less effective overall, particularly in women under 65 years, prompting the cessation of its further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. Buzdar, A., Hayes, D., El-Khoudary, A., et al.[2019]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

References

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

T-DXd Keeps Shining in Breast Cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. [2023]

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

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. [2023]

4. England pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Letrozole in the neoadjuvant setting: the P024 trial. [2021]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Estrogen receptors as therapeutic targets in breast cancer. [2018]

11. Japan pubmed.ncbi.nlm.nih.gov

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]