Dato-DXd for Triple-negative Breast Cancer

Recruiting at 228 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Hormone 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: 26 months

644 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Dato-DXd to see if it works better than current treatments for patients with a specific type of breast cancer that has come back or spread and cannot be treated with certain common therapies. The drug aims to target and kill cancer cells more effectively.

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

The trial requires a 'washout period' (time without taking certain medications) before starting the study. This includes stopping any anti-cancer therapy, including hormonal therapy, for at least 3 weeks, and other specific medications like chloroquine/hydroxychloroquine for more than 14 days. It's best to discuss your current medications with the trial team to see if they need to be stopped.

Is Dato-DXd safe for humans?

In early trials, Dato-DXd showed manageable toxicity, meaning side effects were present but could be controlled, in patients with advanced triple-negative breast cancer. ^{1 2 3 4 5}

What makes the drug Dato-DXd unique for treating triple-negative breast cancer?

Dato-DXd is unique because it is an antibody-drug conjugate that targets TROP-2, a protein often found in triple-negative breast cancer, and delivers a topoisomerase I inhibitor directly to the cancer cells, potentially improving effectiveness and reducing side effects compared to traditional chemotherapy. ^{1 2 4 6 7}

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

Research shows that the drug datopotamab deruxtecan (Dato-DXd) has shown encouraging response rates in patients with advanced triple-negative breast cancer, with 34% experiencing a complete or partial response. Additionally, eribulin, another component of the treatment, has been found to work well with other drugs to kill cancer cells in this type of breast cancer. ^{1 2 4 5 8}

Eligibility Criteria

This trial is for adults with triple-negative breast cancer that's locally recurrent and inoperable or has spread (metastatic), who haven't had chemotherapy for this condition, and can't use PD-1/PD-L1 inhibitor therapy. Participants need at least one measurable tumor lesion, good physical status (ECOG PS 0 or 1), adequate organ function, a life expectancy of over 12 weeks, and must not be pregnant or breastfeeding.

Inclusion Criteria

My cancer is HER2 negative according to specific testing guidelines.

You are expected to live for at least 12 weeks.

I am using birth control as per my local guidelines.

Exclusion Criteria

I have an active tuberculosis infection.

I had cancer before, but it was treated successfully over 3 years ago and is unlikely to come back.

I have not been in any drug studies or had severe reactions to certain drugs recently.

Timeline

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

26 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 weeks post-progression

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Capecitabine
• Carboplatin
• Dato-DXd
• Eribulin mesylate

Trial Overview The study compares Dato-DXd to standard chemotherapies like Paclitaxel and Nab-paclitaxel in patients with advanced triple-negative breast cancer. It's an open-label Phase III trial where participants are randomly assigned to either the test drug group or the control group receiving investigator's choice of chemotherapy.

Participant Groups

Group I: Dato-DXd Experimental Treatment 1 Intervention

Arm 1: Dato-DXd

Group II: Investigator's Choice of Chemotherapy (ICC) Active Control 5 Interventions

Arm 2: If no prior taxane, or prior taxane in the (neo)adjuvant setting and DFI \> 12 months, paclitaxel or nab-paclitaxel If prior taxane and DFI ≤ 12 months: capecitabine, carboplatin, or eribulin.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

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

Findings from Research

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]

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]

DZ-2384, a new microtubule-targeting agent, shows strong effectiveness against triple-negative breast cancer (TNBC) in preclinical models, outperforming traditional taxanes like paclitaxel in terms of reduced toxicity and a wider therapeutic window (14-32 compared to 2.0 for paclitaxel).

DZ-2384 not only effectively reduces brain metastatic lesions but also works synergistically with anti-CTLA-4 immunotherapy, suggesting it could enhance treatment outcomes when combined with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DZ-2384 has a superior preclinical profile to taxanes for the treatment of triple-negative breast cancer and is synergistic with anti-CTLA-4 immunotherapy. Bernier, C., Soliman, A., Gravel, M., et al.[2019]

References

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

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). [2022]

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

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

DZ-2384 has a superior preclinical profile to taxanes for the treatment of triple-negative breast cancer and is synergistic with anti-CTLA-4 immunotherapy. [2019]

5. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer. A meta-analysis of randomized controlled trials. [2018]

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

Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. [2020]

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

The emergence of targeted therapy for HER2-low triple-negative breast cancer: a review of fam-trastuzumab deruxtecan. [2023]

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

Safety evaluation of Datopotamab deruxtecan for triple-negative breast cancer: a meta-analysis. [2023]