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New treatment option for Breast Cancer
Official title TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd
ClinicalTrials.gov ID: NCT06533826
What this study is testing
What is Trastuzumab Deruxtecan?
Trastuzumab Deruxtecan is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for breast cancer.
Also referred to as Enhertu, am-trastuzumab deruxtecan-nxki.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The purpose of this study is to test the safety and effectiveness of the sequence of two investigational drugs (trastuzumab deruxtecan followed by datopotamab deruxtecan, or datopotamab deruxtecan followed by trastuzumab deruxtecan) to learn whether the treatment works in treating HER2-negative (HER2-low or HER2-0) metastatic breast cancer. The names of the study drugs involved in this study are: Datopotamab deruxtecan (a type of antibody drug conjugate) Trastuzumab deruxtecan (a type of antibody drug conjugate)
- Phase 2: a mid-size study of how well it works
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Participants must have histologically or cytologically confirmed invasive breast cancer with unresectable locally advanced or metastatic disease...
- The most recent pathology results will be considered for enrollment according to local testing of ER, PR and HER2 in a CLIA-certified environment...
- Participants must have history of HER2-low or HER2-0 breast cancer per local testing, and no known history of HER2-positive breast cancer. All...
- HER2-low status is defined as IHC 1+ or 2+/ISH non-amplified breast cancer in any prior tumor sample (e.g., primary or metastatic tumor) collected...
- HER2-0 status is defined as IHC 0 (null or ultra-low) in all prior tumor samples with available HER2 pathology results: IHC 0+/ISH- or IHC 0+/ISH...
You likely can't join if
- Concurrent use of any other investigational or study agents that are being used to treat the underlying malignancy.
- Any prior treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I, except as specified per protocol for ADC2 cohorts.
- Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days...
- Clinically significant corneal disease.
- History of severe hypersensitivity reactions to either trastuzumab deruxtecan or datopotamab deruxtecan or their inactive ingredients.
- History of severe hypersensitivity reactions to other monoclonal antibodies.
See the full eligibility criteria
Who can join
- Participants must have histologically or cytologically confirmed invasive breast cancer with unresectable locally advanced or metastatic disease. Participants without pathologic or cytologic confirmation of metastatic...
- The most recent pathology results will be considered for enrollment according to local testing of ER, PR and HER2 in a CLIA-certified environment. ER, PR and HER2 status per local testing must be known prior to study...
- Participants must have history of HER2-low or HER2-0 breast cancer per local testing, and no known history of HER2-positive breast cancer. All available prior HER2 pathology results must be HER2-low or HER2-0; no known...
- HER2-low status is defined as IHC 1+ or 2+/ISH non-amplified breast cancer in any prior tumor sample (e.g., primary or metastatic tumor) collected prior to study enrollment: IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH...
- HER2-0 status is defined as IHC 0 (null or ultra-low) in all prior tumor samples with available HER2 pathology results: IHC 0+/ISH- or IHC 0+/ISH untested (IHC 0+: IHC 0 absent membrane staining [null] or IHC 0 with...
- Participants with any HR status will be allowed on study.
- HR-positive cohorts: ER and/or PR expression ≥1%
- HR-negative cohorts: ER and PR expression \<1%
- All cohorts: The most recent HER2 pathology result must be HER2-0 or HER2-low (i.e., must not be HER2-positive).
- HER2-0: IHC 0+/ISH- or IHC 0+/ISH untested.
- HER2-low: IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested (note: ISH may be determined by either fluorescence in situ hybridization [FISH] or dual in situ hybridization [DISH]).
- Participants must have measurable disease per RECIST 1.1.
- Participants must be willing to undergo research tissue biopsies (at baseline prior to ADC1, after 3 weeks of treatment with ADC1, at progression on ADC1 or baseline prior to ADC2, and at progression on ADC2), if tumor...
- Prior endocrine therapy: Participants with HR-positive breast cancer considered to be candidates for endocrine therapy must have: a) progressed on or within 12 months of adjuvant endocrine therapy or received at least...
- Prior chemotherapy: Prior lines of chemotherapy allowed in the metastatic setting are specified below. Prior topoisomerase I inhibitor therapy is not allowed in any setting, except as specified below for ADC2 cohorts...
- ADC1 T-DXd cohorts: Participants must have progressed on 0-1 prior lines in the metastatic setting.
- ADC1 Dato-DXd cohorts: Participants must have progressed on 0-1 prior lines in the metastatic setting.
- ADC2 T-DXd cohorts: Participants must have progressed on 1-2 prior lines in the metastatic setting, including Dato-DXd (single-agent) as the most recent therapy. Confirmation of documented progressive disease on...
- ADC2 Dato-DXd cohorts: Participants must have progressed on 1-2 prior lines in the metastatic setting, including T-DXd (single-agent) as the most recent therapy. Confirmation of documented progressive disease on T-DXd...
- Prior biologic or targeted therapy: Patients must have discontinued all biologic or targeted therapy (e.g., CDK4/6 inhibitor) at least 14 days prior to study treatment initiation. All toxicities related to prior...
- Prior investigational agents for treatment of cancer: Investigational agents must have been discontinued at least 21 days prior to initiation of study therapy. All toxicities related to prior investigational agents must...
- Prior radiation therapy: Patients may have received prior radiation therapy. Radiation therapy must be completed at least 14 days prior to the initiation of study treatment (at least 7 days for SRS), and all toxicities...
- Patients with history of treated CNS metastases are eligible, provided the following criteria are met:
- Disease outside the CNS is present.
- Prior SRS/SRT or WBRT should be completed ≥ 7 days before study treatment initiation.
- Recovery from acute toxicity associated with the treatment to ≤ CTCAE v5.0 grade 1 or baseline (with the exception of alopecia), with no requirement for escalating doses of corticosteroids over the past 7 days.
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is...
- Participants on bisphosphonates or RANK ligand inhibitors may continue receiving therapy during study treatment and also may initiate therapy with these agents on study if clinically indicated.
- The subject is ≥ 18 years old.
- ECOG performance status 0-1 (Karnofsky \> 60%).
- Participants must have adequate organ and marrow function within 2 weeks prior to study treatment initiation as defined below:
- Absolute neutrophil count ≥1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9.0 g/dl
- INR/PT/aPTT ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy and PT or aPTT is in therapeutic range of anticoagulant
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (or ≤ 3.0 x ULN in patients with documented Gilbert's Syndrome)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN or ≤ 5.0 × institutional ULN for participants with documented liver metastases
- Serum or plasma creatinine ≤ 1.5 × institutional ULN OR creatinine clearance (as calculated using the Cockcroft-Gault equation) ≥ 30 mL/min/ 1.73m2 for participants with creatinine levels above institutional ULN.
- Resolution of all toxicities related to prior anticancer therapy to Grade ≤ 1 or baseline, including toxicities from ADC1 before enrolling to ADC2, unless otherwise specified per protocol.
- For T-DXd cohorts, baseline LVEF ≥ 50% prior to registration, as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive).
- Female people of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to study treatment initiation. Childbearing potential is defined as participants who have not reached a...
- Women of childbearing potential (WOCBP) and the female partners of male participants must agree to use an adequate method of contraception. Contraception is required starting with the first dose of study medication...
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and 4 months after the last dose of study treatment.
- The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document.
What rules you out
- Concurrent use of any other investigational or study agents that are being used to treat the underlying malignancy.
- Any prior treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I, except as specified per protocol for ADC2 cohorts.
- Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention.
- Clinically significant corneal disease.
- History of severe hypersensitivity reactions to either trastuzumab deruxtecan or datopotamab deruxtecan or their inactive ingredients.
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Major surgery within 2 weeks prior to study treatment initiation.
- Uncontrolled, significant intercurrent or recent illness including, but not limited to, ongoing or active infection, uncontrolled non-malignant systemic disease, uncontrolled seizures, or psychiatric illness/social...
- History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening...
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic...
- Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \>450 msec (males).
- Any of the following procedures or conditions in 6 months prior to enrollment: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure (New York Heart...
- Individuals with a history of a second malignancy are ineligible except for the following circumstances:
- Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy.
- Individuals with the following cancers that have been diagnosed and treated within the past 3 years are eligible: cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer of the skin.
- Patients with other cancers diagnosed within the past 3 years and felt to be at low risk of recurrence should be discussed with the study principal investigator to determine eligibility.
- Known human immunodeficiency virus (HIV) infection that is not well controlled.
- Known hepatitis B or C virus infection that is active or uncontrolled.
- Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice).
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in...
- Women who are pregnant or breastfeeding or planning to become pregnant.
The study team makes the final eligibility decision.
Where it's taking place
- Birmingham, Alabama, United States
- San Francisco, California, United States
- New Haven, Connecticut, United States
- Washington D.C., District of Columbia, United States
- Chicago, Illinois, United States
- Boston, Massachusetts, United States
- The Bronx, New York, United States
- Chapel Hill, North Carolina, United States
- Nashville, Tennessee, United States
- Houston, Texas, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Birmingham, Alabama, United States; San Francisco, California, United States; New Haven, Connecticut, United States; Washington D.C., District of Columbia, United States; Chicago, Illinois, United States; Boston, Massachusetts, United States and 4 more location(s). Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.