Dato-DXd +/− Durvalumab vs Chemotherapy + Pembrolizumab for Triple-Negative Breast Cancer
Recruiting in Palo Alto (17 mi)
+214 other locations
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.
12345Is 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.
12367What 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.
1891011Eligibility 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.
+7 more
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.
+13 more
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Dato-DXd + durvalumabExperimental Treatment2 Interventions
Arm 1: Dato-DXd + durvalumab
Group II: Dato-DXdExperimental Treatment1 Intervention
Arm 3: Dato-DXd
Group III: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumabActive Control5 Interventions
Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SitePlantation, FL
Research SiteElmhurst, IL
Research SiteEl Paso, TX
Research SiteDaphne, AL
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-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. [2023]Despite recent treatment advances, the prognosis for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) remains poor. The antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) is composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable, cleavable linker. The phase III TROPION-Breast02 trial in patients previously untreated for locally recurrent inoperable or metastatic TNBC, who are not candidates for PD-1/PD-L1 inhibitors is evaluating efficacy and safety of Dato-DXd versus investigator's choice of chemotherapy (ICC). Approximately 600 patients will be randomized 1:1 to Dato-DXd 6 mg/kg iv. every 3 weeks or ICC (paclitaxel, nab-paclitaxel, carboplatin, capecitabine or eribulin mesylate). Dual primary end points are progression-free survival by blinded independent central review and overall survival.
"Very Compelling" Results for ADC in TNBC Trial. [2022]In a phase I trial, the antibody-drug conjugate datopotamab deruxtecan demonstrated encouraging response rates and manageable toxicity in patients with advanced/metastatic triple-negative breast cancer that has recurred after, or is resistant to, multiple therapies. Overall, 34% of patients experienced a complete or partial response.
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).
Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. [2023]In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial 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.
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.
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.
Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. [2020]PD-1 axis blockade, in combination with chemotherapy, improves outcomes in advanced triple-negative breast cancer that is PD-L1 positive. The phase 3 KEYNOTE-522 trial now shows that the addition of pembrolizumab to chemotherapy improves pathological complete response rates regardless of PD-L1 status and appears to improve survival.
Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. [2022]Breast cancer is the most common cause of cancer-related deaths among women. There are a limited number of targeted therapies available for triple-negative breast cancer (TNBC), and chemotherapy is the mainstay of treatment. Among checkpoint inhibitors, atezolizumab is the only drug approved for PD-L1+ TNBC patients. We performed a systematic review to assess the efficacy and safety of PD-1 inhibitor pembrolizumab in triple-negative breast cancer. We included 15 clinical trials in this review. Pembrolizumab was well tolerated by all patients with triple-negative breast cancer. Pembrolizumab was more effective in the treatment of early-stage TNBC patients as compared to placebo, regardless of PD-L1 status. In advanced-stage breast cancer, pembrolizumab was as effective as single-agent chemotherapy with a better safety profile. Pembrolizumab with chemotherapy showed significantly better median progression free survival as compared to chemotherapy in advanced TNBC.
Neoadjuvant Pembrolizumab Takes on TNBC. [2020]Pembrolizumab plus chemotherapy may be an effective neoadjuvant treatment for triple-negative breast cancer. In the phase III KEYNOTE-522 trial, patients treated with the PD-1 inhibitor in combination with chemotherapy prior to surgery were more likely to have a pathologic complete response than patients who received chemotherapy alone, regardless of PD-L1 levels.
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]Pembrolizumab is approved for the neoadjuvant/adjuvant treatment of early triple-negative breast cancer (TNBC) patients in combination with chemotherapy. The Keynote-522 trial used platinum chemotherapy. As neoadjuvant nab-paclitaxel (nP) is also highly effective in triple-negative breast cancer patients, this study investigates the response to nP-containing neoadjuvant chemotherapy in combination with pembrolizumab.