Dato-DXd + Durvalumab for Breast Cancer
Recruiting in Palo Alto (17 mi)
+270 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must not be taking: Hormone therapy
Disqualifiers: Autoimmune disorders, Hepatitis, HIV, others
Stay on Your Current Meds
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative 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 those using systemic hormone replacement therapy or oral hormonal contraception. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Dato-DXd + Durvalumab for breast cancer?
The TROPION-Breast01 study is evaluating the effectiveness of Dato-DXd in patients with inoperable or metastatic HR+/HER2- breast cancer, suggesting it may be a promising option for those who have limited treatment choices beyond chemotherapy.
12345Is the combination of Dato-DXd and Durvalumab safe for breast cancer treatment?
The safety of Datopotamab deruxtecan (Dato-DXd) is being evaluated in ongoing studies for breast cancer, and it is considered a promising treatment option. While specific safety data for the combination with Durvalumab is not provided, Dato-DXd has shown manageable safety in other studies.
12567What makes the Dato-DXd + Durvalumab treatment unique for breast cancer?
The Dato-DXd + Durvalumab treatment is unique because it combines an antibody-drug conjugate (Dato-DXd) with an immune checkpoint inhibitor (Durvalumab), potentially enhancing the immune system's ability to target and destroy cancer cells. This combination approach is novel compared to traditional chemotherapy, which does not typically involve immune system modulation.
89101112Eligibility Criteria
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.
+3 more
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.
+10 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Dato-DXd plus durvalumabExperimental Treatment9 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 chemotherapyActive Control8 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteGoodyear, AZ
Research SiteFort Myers, FL
Research SiteSaint Petersburg, FL
Research SiteIrvine, CA
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
Daiichi Sankyo, Inc.Industry Sponsor
Daiichi SankyoIndustry Sponsor
References
TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. [2023]Improving the prognosis for patients with metastatic HR+/HER2- breast cancer remains an unmet need. Patients with tumors that have progressed on endocrine therapy and/or are not eligible for endocrine therapy had limited treatment options beyond chemotherapy. Antibody-drug conjugates are a novel and promising treatment class in this setting. Datopotamab deruxtecan (Dato-DXd) consists of a TROP2-directed humanized IgG1 monoclonal antibody attached via a serum-stable cleavable linker to a topoisomerase I inhibitor payload. TROPION-Breast01 is an ongoing phase 3 study that is evaluating the efficacy and safety of Dato-DXd compared with investigator's choice of standard-of-care chemotherapy in patients with inoperable or metastatic HR+/HER2- breast cancer who have received one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting. Clinical Trial Registration: NCT05104866 (ClinicalTrials.gov).
Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. [2023]Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population.
T-DXd Keeps Shining in Breast Cancer. [2023]The latest phase III data from DESTINY-Breast02 and DESTINY-Breast03 indicate that trastuzumab deruxtecan, or T-DXd, outperforms capecitabine-based chemotherapy and T-DM1 in patients with metastatic HER2-positive breast cancer. According to results from an investigator-initiated trial, TRIO-US B-12 TALENT, T-DXd may also have neoadjuvant potential in HER2-low disease.
Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01). [2023]Primary analysis of the multicenter, open-label, single-arm, phase 2 DESTINY-Breast01 trial (median follow-up, 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with median follow-up of 26.5 months (data cutoff, March 26, 2021).
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]In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior progression-free survival and overall survival versus trastuzumab emtansine (T-DM1) and manageable safety in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer. Here, patient-reported outcomes (PROs) are reported along with hospitalization data.
Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. [2023]This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data.
Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. [2022]Introduction: Trastuzumab deruxtecan (T-DXd) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate with a humanized anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload. The phase II trial DESTINY-Gastric01 has demonstrated that T-DXd exhibits antitumor activity in patients with HER2-positive advanced gastric cancer (AGC) who had received at least two previous therapies, including trastuzumab.Area covered: T-DXd was approved for previously treated HER2-positive AGC in Japan. The US Food and Drug Administration also approved on 15 January 2021. In this article, we review the development of T-DXd, its pharmacology, and its safety profile in patients with HER2-positive AGC.Expert opinion: T-DXd has demonstrated a significantly higher objective response rate and a longer overall survival in HER2-positive AGC patients with two or more previous lines of systemic chemotherapy, including trastuzumab. Safety profile was acceptable. Currently, there are several ongoing clinical trials of T-DXd in combination with cytotoxic chemotherapy or an immune checkpoint inhibitor.
Durvalumab: First Global Approval. [2022]Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Durvalumab ± tremelimumab is under phase III clinical trials in urothelial carcinoma, non-small cell lung cancer, small cell lung cancer and head and neck squamous cell carcinoma. The drug is also being evaluated in phase I or II clinical trials in a wide range of solid tumours and haematological malignancies. This article summarizes the milestones in the development of durvalumab leading to this first approval for urothelial carcinoma.
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. [2023]MEDI0680 is a humanized anti-programmed cell death-1 (PD-1) antibody, and durvalumab is an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity and safety of MEDI0680 plus durvalumab versus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal cell carcinoma who received at least one prior line of antiangiogenic therapy.
Durvalumab for the treatment of non-small cell lung cancer. [2019]In non-small cell lung cancer (NSCLC), immunotherapy is one of today's most important and ground-breaking systemic treatments, mainly represented by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2. Areas covered: In advanced NSCLC patients, durvalumab has demonstrated activity and acceptable tolerability, particularly with ≥25% PD-L1 tumor expression in the EGFR and ALK wild-type population. However, preliminary data have shown lower efficacy in EGFR mutant and ALK-positive patients. The results from the recent PACIFIC study in locally advanced patients have placed durvalumab as standard of care in consolidation after chemoradiation, leading to Food and Drug Administration (FDA) approval. Expert commentary: Early data suggest promising activity for durvalumab with the CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in combination with other drugs such as platinum-doublet chemotherapy. However, treatment-related toxicity associated with the combinations is an important aspect of the benefit-risk evaluation in the decision-making process. Results of ongoing phase III trials will provide illuminating data to confirm the place of durvalumab in the management of NSCLC patients.
Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. [2021]The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.