Dato-DXd +/− Durvalumab for Breast Cancer

Not currently recruiting at 276 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with triple-negative breast cancer (TNBC) that remains after initial therapy and surgery. Researchers are testing a drug called Dato-DXd (Datopotamab deruxtecan) alone and in combination with another drug, Durvalumab, to evaluate their effectiveness compared to standard treatments. The study targets individuals with TNBC and residual disease post-surgery and prior chemotherapy, without any cancer spread to other body parts. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants an opportunity to contribute to a treatment nearing widespread availability.

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.

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

Research has shown that Dato-DXd is generally safe for treating breast cancer. In studies with patients who had advanced breast cancer, most tolerated Dato-DXd well. Some patients experienced side effects, but serious ones were less common.

When combined with Durvalumab, a type of immune therapy, Dato-DXd also proved safe. The combination did not significantly increase severe side effects. These findings suggest that both Dato-DXd alone and with Durvalumab are generally safe options for breast cancer patients.

However, each person's experience can differ. Participants should discuss potential risks and benefits with their doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which often involve chemotherapy or hormone therapies, Dato-DXd is unique because it is an antibody-drug conjugate specifically designed to target and deliver chemotherapy directly to cancer cells, minimizing damage to healthy cells. This targeted approach could potentially reduce side effects compared to traditional chemotherapy. Moreover, when Dato-DXd is combined with Durvalumab, an immune checkpoint inhibitor, it may enhance the body's immune response against cancer cells, offering a novel dual-action treatment strategy. Researchers are excited about these features as they could improve the effectiveness and tolerability of breast cancer treatments compared to existing options.

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

Research has shown that Dato-DXd, one of the treatments in this trial, may help treat triple-negative breast cancer (TNBC). In earlier studies, it significantly increased the time patients lived and delayed disease worsening, reducing the risk of progression or death by 43%. In this trial, some participants will receive Dato-DXd alone, while others will receive it with Durvalumab. Another study found that combining Dato-DXd with Durvalumab led to significant tumor shrinkage in 79% of patients. These findings suggest that Dato-DXd, either alone or with Durvalumab, could be a helpful option for people with TNBC. ^{1 2 3 4 6}

Who Is on the Research Team?

Aditya Bardia, MD, MPH

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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]

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) 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]

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]

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]

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]

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]

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]

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]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/DATROWAY-datopotamab-deruxtecan-dlnk-demonstrated-an-unprecedented-median-overall-survival-improvement-of-five-months-vs-chemotherapy-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-TROPION-Breast02.html

DATROWAY® (datopotamab deruxtecan-dlnk) ... DATROWAY® (datopotamab deruxtecan-dlnk) demonstrated an unprecedented median overall survival improvement of five months vs. chemotherapy as 1st ...

2. onclive.com onclive.com/view/tropion-breast02-data-support-dato-dxd-as-new-first-line-soc-in-triple-negative-breast-cancer

TROPION-Breast02 Data Support Dato-DXd as New First- ... Dato-DXd significantly improved OS and PFS in TNBC patients not eligible for immunotherapy, reducing disease progression risk by 43% and death ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12393668/

Datopotamab deruxtecan-dlnk for treatment of patients with ... The OS endpoint was not met; at the final analysis (FA) of OS, the median OS was 18.6 months in the Dato-DXd arm and 18.3 months in the ICC arm ...

4. datrowayhcp.com datrowayhcp.com/hr-positive-her2-negative-mbc/efficacy/efficacy-data

TROPION-Breast01 Efficacy Data - Datroway See efficacy data from the TROPION-Breast01 trial of DATROWAY®, including PFS & OS, ORR, DoR, and PFS by subgroup. Please see full Prescribing Information ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00920

Primary Results From TROPION-Breast01 In this primary analysis, TROPION-Breast01 met its dual primary PFS end point; Dato-DXd reduced the risk of disease progression or death by 37% ...

6. daiichisankyo.com daiichisankyo.com/files/news/pressrelease/pdf/202409/20240923_E.pdf

Datopotamab Deruxtecan Final Overall Survival Results ... “Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in. TROPION-Breast01, a result ...