Dato-DXd + Durvalumab for Breast Cancer

Not currently recruiting at 314 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Hormone therapy

Disqualifiers: Autoimmune disorders, Hepatitis, HIV, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for certain types of breast cancer that have not been treated before. It compares two treatment plans: one uses the drugs Dato-DXd (datopotamab deruxtecan, an experimental treatment) and durvalumab, while the other uses pembrolizumab with chemotherapy. The goal is to determine which plan more effectively fights breast cancer, specifically TNBC (triple-negative breast cancer) or hormone receptor-low/HER2-negative types. Individuals with these types of breast cancer and no history of prior invasive breast cancer may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute 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 those using systemic hormone replacement therapy or oral hormonal contraception. It's best to discuss your specific medications with the trial team.

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

Research has shown that Dato-DXd, when combined with durvalumab, is generally safe. Although side effects were common, most were mild to moderate. Serious side effects occurred less frequently, suggesting that most people can tolerate the combination well.

Pembrolizumab's safety is well-established, as it is already used to treat various cancers. It is usually safe, though some individuals might experience fatigue or mild reactions.

Overall, both treatment options in the study are manageable for most patients. However, like any treatment, risks exist, so discussing these with the study team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle breast cancer. Dato-DXd is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially increasing its effectiveness and reducing side effects compared to traditional chemotherapy. Durvalumab and pembrolizumab are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells, offering a different approach than standard chemotherapy. Additionally, these treatments are being tested in combination, which could enhance their effectiveness and provide new hope for patients with difficult-to-treat breast cancer.

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

In this trial, participants will receive either the combination of Dato-DXd and durvalumab or pembrolizumab with chemotherapy. Previous studies have shown promising results for the combination of Dato-DXd and durvalumab in treating breast cancer. Specifically, one study found that Dato-DXd helped patients with triple-negative breast cancer (TNBC) live five months longer than those who received chemotherapy. This combination also demonstrated lasting effectiveness in the initial treatment of metastatic TNBC, continuing to work well over time. Additionally, Dato-DXd reduced the risk of disease progression or death by 37%. These findings suggest that this treatment could be effective for people with TNBC or hormone receptor-low/HER2-negative breast cancer. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with Stage II or III breast cancer that's triple-negative or hormone receptor-low/HER2-negative can join. They need good bone marrow and organ function, an ECOG performance status of 0 or 1, a tumor sample for testing, and must follow local contraception rules.

Inclusion Criteria

My breast cancer is confirmed to be at Stage II or III and is either triple-negative or has low hormone receptors and is HER2-negative.

I am fully active or restricted in physically strenuous activity but can do light work.

My bone marrow and organs are functioning well.

Exclusion Criteria

I had cancer before, but it was treated successfully over 3 years ago with no current signs of return.

My cancer has spread to parts of my body far from where it started.

My HIV infection is not well controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with either Dato-DXd plus durvalumab or pembrolizumab plus chemotherapy prior to surgery

24 weeks

Every 3 weeks (Q3W) visits

Surgery

Participants undergo definitive surgery to assess pathologic complete response

Adjuvant Treatment

Participants receive adjuvant therapy with durvalumab or pembrolizumab, with optional chemotherapy for those with residual disease

27 weeks

Every 3 weeks (Q3W) visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide, Doxorubicin, Epirubicin, Paclitaxel, Carboplatin, Capecitabine
• Dato-DXd
• Durvalumab
• Olaparib
• Pembrolizumab

Trial Overview The study compares two treatments: Dato-DXd plus durvalumab (with/without chemo) versus pembrolizumab plus chemotherapy (with/without more chemo), both before and after surgery in patients who haven't had prior treatment for their breast cancer.

How Is the Trial Designed?

Group I: Dato-DXd plus durvalumab Experimental Treatment 9 Interventions

Participants receive durvalumab every 3 weeks (Q3W) + Dato-DXd Q3W as neoadjuvant therapy prior to surgery; followed by 9 cycles of durvaluamb Q3W as adjuvant therapy post-surgery. Adjuvant chemotherapy may be given in combination with durvalumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease Adjuvant chemotherapy may be one of these: 1. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) and carboplatin (weekly or Q3W) for 4 cycles (12 weeks); 2. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks); 3. Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks); 4. Capecitabine (Q3W) for 8 cycles.

Group II: Pembrolizumab plus chemotherapy Active Control 8 Interventions

Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Adjuvant capecitabine (Q3W) for 8 cycles may be given in combination with pembrolizumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease.

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 safety run-in of the IMMUNOBIL PRODIGE 57 trial involving 20 patients, the combination of durvalumab and tremelimumab with paclitaxel resulted in a high rate of dose-limiting toxicities (50%), including serious anaphylactic reactions and other severe adverse events.

Due to the safety concerns raised by the combination therapy, the trial will proceed with only the durvalumab and tremelimumab combination, indicating that the addition of paclitaxel may not be safe for patients with advanced biliary tract carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Boilève, A., Hilmi, M., Gougis, P., et al.[2021]

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]

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]

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]

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]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[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]

In the DESTINY-Breast01 trial with 184 patients, trastuzumab deruxtecan (T-DXd) showed a confirmed objective response rate of 62.0% and a median overall survival of 29.1 months, indicating its effectiveness in treating HER2-positive metastatic breast cancer after previous treatment with trastuzumab emtansine.

While T-DXd demonstrated sustained antitumor activity, it also had a notable safety profile, with 99.5% of patients experiencing drug-related adverse events, including a 15.8% incidence of interstitial lung disease/pneumonitis, highlighting the importance of monitoring for serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01). Saura, C., Modi, S., Krop, I., et al.[2023]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

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]

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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. 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 ...

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Datopotamab deruxtecan plus Imfinzi demonstrated robust ... Results showed that datopotamab deruxtecan plus Imfinzi, an anti-PD-L1 therapy, demonstrated a confirmed objective response rate (ORR) of 79%.

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