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TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd

ConditionsBreast CancerHER2-low Breast CancerMetastatic Breast CancerHER2-negative Breast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAna C Garrido-Castro, MD

About this trial

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)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation; i.e., visible chest wall disease or metastases on imaging meeting standard radiology criteria (i.e., lymph nodes larger than 1 cm in the short axis diameter).

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 registration.

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 IHC 3+ or ISH-amplified breast cancer is allowed.

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 untested (note: ISH may be determined by either fluorescence in situ hybridization [FISH] or dual in situ hybridization [DISH])

Disqualifiers

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.

Trial design

Design model

Crossover

Treatments tested in this trial

  • Trastuzumab Deruxtecan

    Drug

    A HER2-directed ADC, 100mg/vial, via intravenous (into the vein) infusion per protocol.

  • Datopotamab Deruxtecan

    Drug

    A TROP2-directed antibody drug conjugate, 100mg/vial, via intravenous (into the vein) infusion per protocol.

Treatment groups

357 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Arm A (ADC1 T-DXd HR+)Experimental treatment 1 intervention
Group B: Arn B (ADC1 T-DXd HR-)Experimental treatment 1 intervention
Group C: Arm C (ADC1 Dato-DXd HR+)Experimental treatment 1 intervention
Group D: Arm D (ADC1 Dato-DXd HR-)Experimental treatment 1 intervention
Group E: Arm E (ADC2 Dato-DXd HR+)Experimental treatment 1 intervention
Group F: Arm F (ADC2 Dato-DXd HR-)Experimental treatment 1 intervention
Group G: Arm G (ADC2 T-DXd HR+)Experimental treatment 1 intervention
Group H: Arm H (ADC2 T-DXd HR-)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Objective Response Rate in ADC1 (Group 1) Cohort

Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined per protocol.

Time frame
The observation period related to this endpoint is up to 36 months.
2

Objective Response Rate in ADC2 (Group 2) Cohort

Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined per protocol.

Time frame
The observation period related to this endpoint is up to 36 months.

Secondary outcomes

1

Median Progression Free Survival in ADC1 (Group 1) Cohort

PFS based on Kaplan-Meier methodology will be defined as the time from randomization until the identification of disease progression or death, whichever occurs first. Subjects without disease progression or death at the time of analysis will be censored at the date of last disease evaluation.

Time frame
The observation period related to this endpoint is up to 36 months.
2

Median Overall Survival (OS) in ADC1 (Group 1) Cohort

Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

Time frame
The observation period related to this endpoint is up to 5 years.
3

Clinical Benefit Rate (CBR) in ADC1 (Group 1) Cohort

Clinical Benefit Rate (CBR) is defined as the proportion of participants with CR, PR and stable disease (SD) for ≥ 24 weeks as the best overall response.

Time frame
The observation period related to this endpoint is up to 36 months.
4

Time to Progression (TTP) in ADC1 (Group 1) Cohort

Time to Progression (TTP) is defined as the time from registration to ADC1 to progression, or censored at date of last disease evaluation for those without progression reported based on Kaplan-Meier methodology.

Time frame
The observation period related to this endpoint is up to 36 months.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ana C Garrido-Castro, MD

Lead sponsor

Dana-Farber Cancer Institute

Sponsor institution

AstraZeneca

Collaborator

Translational Breast Cancer Research Consortium

Collaborator

Source ClinicalTrials.gov
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