Dato-DXd +/− Durvalumab vs Chemotherapy + Pembrolizumab for Triple-Negative Breast Cancer

Recruiting at 258 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Corticosteroids, Anticonvulsants, Antivirals, others

Disqualifiers: Uncontrolled infection, Active hepatitis, 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: 33 months

625 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatment options for individuals with triple-negative breast cancer (TNBC) that cannot be surgically removed or has metastasized. Researchers compare the effects of a new drug, Dato-DXd, alone or with durvalumab, against standard chemotherapy paired with pembrolizumab. Participants should have TNBC positive for the protein PD-L1 and should not have received prior treatment for their cancer in its current form. Those with recurring TNBC who meet these criteria might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are on any concurrent anti-cancer treatment. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

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

Research has shown that Dato-DXd is generally safe. In studies, many participants experienced side effects, but most were not serious. Serious side effects occurred less frequently, indicating that Dato-DXd is usually well-tolerated.

When combined with durvalumab, Dato-DXd remains safe. Studies have demonstrated good results, with side effects typically not severe. Although some serious side effects were reported, they were rare.

For pembrolizumab, already approved for other cancers, safety has been well-researched. Most patients experience mild side effects, though some may encounter more serious ones.

Overall, research supports that these treatments, whether used alone or together, are generally safe for patients, with most side effects being mild to moderate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for triple-negative breast cancer because they offer new approaches compared to the standard chemotherapy options. Dato-DXd is unique because it combines an antibody with a potent chemotherapy agent, directly targeting cancer cells more precisely and potentially reducing side effects. Durvalumab and pembrolizumab, both immune checkpoint inhibitors, work by boosting the immune system's ability to fight cancer, offering a different mechanism than traditional chemotherapy. Together, these treatments could provide more effective options with potentially fewer side effects, making them promising candidates for improving outcomes in this challenging cancer type.

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

Research has shown that Dato-DXd holds promise for treating triple-negative breast cancer (TNBC). Studies have found that it significantly extends patient survival and delays disease progression, reducing the risk of cancer worsening by 43%. In this trial, some participants will receive Dato-DXd alone, while others will receive it with durvalumab, a medicine that enhances the immune system's ability to fight cancer. This combination has demonstrated high success rates in patients with advanced TNBC and maintains effectiveness over a longer period. These findings suggest that Dato-DXd, either alone or with durvalumab, could be effective options for managing TNBC. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with PD-L1 positive triple-negative breast cancer that's locally recurrent and inoperable or has spread (metastatic). They should not have had prior chemo or targeted therapy for their advanced disease, must have measurable disease per specific criteria, and proper organ function. Participants need to agree to use contraception if they can have children.

Inclusion Criteria

My bone marrow and organs are functioning well.

I can provide a tissue sample from my cancer that cannot be removed by surgery.

You have a disease that can be measured using a specific set of guidelines.

Exclusion Criteria

My HIV infection is not well controlled.

I have a serious heart condition that is not under control.

I do not have severe illnesses, recent organ transplants, bleeding disorders, infections, or major heart or mental health issues.

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 of chemotherapy in combination with pembrolizumab

33 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 weeks post-progression

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

64 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Dato-DXd
• Durvalumab
• Gemcitabine
• Nab-paclitaxel
• Paclitaxel
• Pembrolizumab

Trial Overview The study compares the effectiveness of Dato-DXd alone or combined with Durvalumab against standard chemotherapy paired with Pembrolizumab. It's a Phase III trial where patients are randomly assigned to one of these three treatment groups to see which works best.

How Is the Trial Designed?

Group I: Dato-DXd + durvalumab Experimental Treatment 2 Interventions

Arm 1: Dato-DXd + durvalumab

Group II: Dato-DXd Experimental Treatment 1 Intervention

Arm 3: Dato-DXd

Group III: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab Active Control 5 Interventions

Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)

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, 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

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

Published Research Related to This Trial

In the phase III KEYNOTE-522 trial, pembrolizumab combined with chemotherapy showed increased effectiveness as a neoadjuvant treatment for triple-negative breast cancer, leading to a higher rate of pathologic complete response compared to chemotherapy alone.

This benefit was observed regardless of the PD-L1 expression levels in patients, suggesting that pembrolizumab may be a broadly effective option for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

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]

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 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]

The phase 3 KEYNOTE-522 trial demonstrated that adding pembrolizumab, a PD-1 axis blocker, to chemotherapy significantly improves pathological complete response rates in patients with advanced triple-negative breast cancer, regardless of their PD-L1 status.

This combination therapy not only enhances treatment effectiveness but also appears to improve overall survival rates for patients with this aggressive form of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. Savas, P., Loi, S.[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]

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]

Pembrolizumab, a PD-1 inhibitor, was found to be well tolerated and more effective than placebo in treating early-stage triple-negative breast cancer (TNBC), regardless of PD-L1 status, based on a systematic review of 15 clinical trials.

In advanced-stage TNBC, pembrolizumab demonstrated similar efficacy to single-agent chemotherapy but with a better safety profile, and when combined with chemotherapy, it significantly improved median progression-free survival compared to chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. Ali, MA., Aiman, W., Shah, SS., et al.[2022]

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]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

In a phase II trial involving 50 patients with early triple-negative breast cancer, 66% achieved a pathological complete response (pCR) after treatment with nab-paclitaxel and pembrolizumab, indicating a promising efficacy of this combination therapy.

The treatment was associated with manageable side effects, with fatigue, peripheral sensory neuropathy, and neutropenia being the most common adverse events, suggesting that this regimen could be a viable alternative to platinum-based chemotherapy for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Fasching, PA., Hein, A., Kolberg, HC., 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. targetedonc.com targetedonc.com/view/dato-dxd-delivers-significant-tnbc-survival-benefits-in-phase-3-trial

Dato-DXd Delivers Significant TNBC Survival Benefits in ... Dato-DXd significantly improves overall and progression-free survival in first-line treatment of metastatic TNBC without immunotherapy options.

4. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/datroway-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 demonstrated an unprecedented median overall ... Datroway demonstrated an unprecedented median overall survival improvement of five months vs. chemotherapy as 1st-line treatment for patients ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01909

Datopotamab Deruxtecan in Advanced or Metastatic HR+ ... The median progression-free survival in patients with HR+/HER2– BC and TNBC was 8.3 and 4.4 months, respectively. All-cause treatment-emergent ...

6. 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 ...