Dato-DXd for Breast Cancer

(TB-01 Trial)

Not currently recruiting at 210 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Hormonal replacement therapy

Disqualifiers: Uncontrolled infection, Hepatitis B/C, HIV, others

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: Unknown

Duration: 21 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Dato-DXd (Datopotamab deruxtecan) for breast cancer that cannot be surgically removed or has spread to other parts of the body. The study compares Dato-DXd with commonly used chemotherapy drugs to determine which is more effective and safer for patients. It targets those with HR-positive, HER2-negative breast cancer who have already undergone one or two chemotherapy treatments. Eligible participants have experienced cancer progression despite previous treatments and have at least one tumor not treated with radiation. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a required washout period (time without taking certain medications) for previous anticancer therapies before starting 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 and manageable. In earlier studies, patients taking Dato-DXd experienced a significant improvement in the time their cancer did not worsen. Most reported side effects were not severe, though some patients did experience more serious side effects, as is common with many cancer treatments. Overall, current data considers the treatment well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy options like Capecitabine, Gemcitabine, Eribulin mesylate, and Vinorelbine for breast cancer, Dato-DXd is an experimental treatment that works by targeting a specific protein on cancer cells called HER2. This targeted approach allows Dato-DXd to deliver chemotherapy directly to the cancer cells, potentially reducing damage to healthy cells and improving the treatment's effectiveness. Researchers are excited because Dato-DXd could offer a more precise and potentially less toxic alternative to traditional chemotherapy, providing new hope for patients who have limited options.

What evidence suggests that Dato-DXd might be an effective treatment for breast cancer?

Research shows that datopotamab deruxtecan (Dato-DXd), which participants in this trial may receive, can help treat certain types of breast cancer. In earlier studies, Dato-DXd reduced the risk of cancer progression or death by 37% for patients with specific breast cancer types, slowing the cancer's growth. The treatment also extended the time patients lived without the cancer worsening. Although one study did not find a significant difference in overall survival compared to standard treatments, Dato-DXd remains promising for managing difficult-to-treat breast cancer. Another arm of this trial will involve the investigator's choice of chemotherapy, including options like Capecitabine, Gemcitabine, Eribulin, and Vinorelbine. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with inoperable or metastatic HR-positive, HER2-negative breast cancer who have tried 1-2 chemotherapy lines and aren't suitable for endocrine therapy. They must be well enough (ECOG PS of 0 or 1), have adequate organ function, no severe heart conditions, controlled blood pressure, and not pregnant. Participants need a measurable lesion that's RECIST 1.1 compliant and can't have active brain metastases requiring steroids.

Inclusion Criteria

I can care for myself and have not gotten worse in the past 2 weeks.

Has had an adequate treatment washout period before Cycle 1 Day 1, defined as: Major surgery: ≥ 3 weeks, Radiation therapy including palliative radiation to chest: ≥ 4 weeks (palliative radiation therapy to other areas ≥ 2 weeks), Anticancer therapy including hormonal therapy: ≥ 3 weeks (for small molecule targeted agents: ≥ 2 weeks or 5 half-lives, whichever is longer), Antibody-based anticancer therapy: ≥ 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases), Immunotherapy (non-antibody-based therapy): ≥ 2 weeks or 5 times the terminal elimination T½ of the agent, whichever is longer, Chloroquine/hydroxychloroquine: > 14 days, Have available a FFPE tumor sample (block preferred, or a minimum of 20 freshly cut slides), at the time of screening. Note: Sample collection in China will comply with local regulatory approval, Minimum life expectancy of 12 weeks at screening

My blood, liver, kidney, and heart functions meet the trial's requirements.

Exclusion Criteria

I do not have serious heart problems or very high blood pressure.

I had cancer before, but it was treated over 3 years ago and is not likely to come back.

I do not have active or uncontrolled hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Dato-DXd or investigator's choice of chemotherapy

21 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Dato-DXd
• Eribulin
• Gemcitabine
• Vinorelbine

Trial Overview The trial is testing Dato-DXd against standard single-agent chemotherapies like eribulin, capecitabine, vinorelbine, or gemcitabine in patients with certain advanced breast cancers. It aims to see if Dato-DXd is safer or more effective compared to these existing treatments.

How Is the Trial Designed?

Group I: Dato-DXd Experimental Treatment 1 Intervention

Arm 1: Dato-DXd

Group II: Investigators Choice of Chemotherapy (ICC) Active Control 4 Interventions

Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine

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

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

In a phase I trial, datopotamab deruxtecan showed promising response rates, with 34% of patients with advanced or metastatic triple-negative breast cancer experiencing a complete or partial response.

The treatment was found to have manageable toxicity, indicating it may be a safe option for patients who have not responded to multiple previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Very Compelling" Results for ADC in TNBC Trial. [2022]

In a study of 99 patients with non-small cell lung cancer (NSCLC), the combination of docetaxel (DTX) and ramucirumab (Ram) significantly improved progression-free survival (PFS) in patients who had previously received anti-PD-1/L1 therapy, with a median PFS of 5.9 months compared to 2.8 months for DTX alone.

In patients who had not received anti-PD-1/L1 therapy, there was no significant difference in PFS or overall survival (OS) between those treated with DTX alone and those treated with DTX plus Ram, suggesting that Ram may specifically enhance DTX efficacy after prior immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment. Tozuka, T., Kitazono, S., Sakamoto, H., 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]

The phase III DESTINY-Breast04 trial demonstrated that trastuzumab deruxtecan (T-DXd) is effective for patients with inoperable or metastatic HER2-low breast cancer, providing a new treatment option for this group.

Given the limited treatment options available for patients with HER2-low breast cancer, T-DXd is recommended as a new standard of care, highlighting its significance in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd: New Standard for HER2-Low Breast Cancer. [2022]

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]

The study evaluated the cost-effectiveness of pegfilgrastim (Peg-G) for preventing febrile neutropenia in patients with non-small cell lung cancer receiving ramucirumab plus docetaxel, finding that Peg-G increased quality-adjusted life years (QALYs) but was not cost-effective in Japan, with an incremental cost-effectiveness ratio (ICER) of 97,519 USD per QALY gained.

The analysis indicated that Peg-G would only be considered cost-effective if the risk of febrile neutropenia without prophylaxis exceeded 51% or if the cost of Peg-G fell below 649 USD per injection, highlighting the importance of FN risk in determining the economic viability of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of pegfilgrastim in patients with non-small cell lung cancer receiving ramucirumab plus docetaxel in Japan. Kondo, Y., Tachi, T., Sakakibara, T., 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]

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) ... AstraZeneca and Daiichi Sankyo's DATROWAY also demonstrated a highly statistically significant and clinically meaningful 43% reduction in ...

2. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/datopotamab-deruxtecan-final-overall-survival-results-reported-in-patients-with-metastatic-hr-positive-her2-low-or-negative-breast-cancer-in-tropion-breast01-phase-iii-trial.html

Datopotamab deruxtecan final overall survival results ... Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple ...

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. 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% ...

5. 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 ...

6. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/DATROWAY-datopotamab-deruxtecan-dlnk-demonstrated-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-as-1st-line-therapy-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-TROPION-Breast02.html

DATROWAY® (datopotamab deruxtecan-dlnk) ... The safety profile of DATROWAY was consistent with previous clinical trials of DATROWAY in breast cancer. These data will be presented at an ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39265124/

Primary Results From TROPION-Breast01 - PubMed - NIH Conclusion: Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile ...

8. onclive.com onclive.com/view/dato-dxd-could-alter-first-line-soc-in-immunotherapy-ineligible-tnbc

Dato-DXd Could Alter First-Line SOC in Immunotherapy ... Additionally, patients in the Dato-DXd arm achieved a median overall survival (OS) of 23.7 months (95% CI, 19.8-25.6) compared with 18.7 months ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2468294223000977

Safety evaluation of Datopotamab deruxtecan for triple ... The pooled results suggests that Dato-DXd is associated with a favorable safety profile: while any grade treatment-related toxicities were common, grade 3-4 ...