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

Recruiting at 214 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

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

Disqualifiers: Uncontrolled infection, Active hepatitis, HIV, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new drug combination for advanced breast cancer patients whose cancer has returned or spread. It compares the new drugs to standard chemotherapy to see if they help patients live longer without their cancer getting worse. The new treatment aims to kill cancer cells directly and help the immune system fight the cancer. Lapatinib is a novel drug currently being tested in advanced breast cancer.

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.

What data supports the effectiveness of the drug combination Dato-DXd and Durvalumab for treating triple-negative breast cancer?

In a phase I trial, the drug datopotamab deruxtecan (Dato-DXd) showed encouraging response rates, with 34% of patients experiencing a complete or partial response in advanced/metastatic triple-negative breast cancer. Additionally, pembrolizumab combined with chemotherapy demonstrated superior efficacy compared to chemotherapy alone in patients with PD-L1 positive tumors in the KEYNOTE-355 trial. ^{1 2 3 4 5}

Is the treatment Dato-DXd +/− Durvalumab vs Chemotherapy + Pembrolizumab safe for humans?

In a phase I trial, datopotamab deruxtecan (Dato-DXd) showed manageable safety in patients with advanced triple-negative breast cancer, meaning the side effects were considered acceptable. This suggests it is generally safe for human use in this context. ^{1 2 3 6 7}

What makes the drug combination of Dato-DXd, Durvalumab, and Pembrolizumab unique for treating triple-negative breast cancer?

This drug combination is unique because it combines Dato-DXd, an antibody-drug conjugate targeting TROP2, with immunotherapy drugs Durvalumab and Pembrolizumab, which block proteins that prevent the immune system from attacking cancer cells. This approach aims to enhance the immune response against cancer while directly targeting cancer cells, offering a novel strategy for treating triple-negative breast cancer. ^{1 8 9 10 11}

Eligibility Criteria

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.

Trial 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 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

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Dato-DXd (Antitumor Antibiotic)
• Durvalumab (Monoclonal Antibodies)
• Gemcitabine (Chemotherapy)
• Nab-paclitaxel (Chemotherapy)
• Paclitaxel (Chemotherapy)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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 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 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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. England 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. [2023]

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

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

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

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

7. 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]

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

Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. [2020]

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

Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. [2022]

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

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

11. England 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). [2023]