A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer (DB-07)

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ClinicalTrials.gov Identifier: NCT04538742

Recruitment Status : Recruiting

First Posted : September 4, 2020

Last Update Posted : February 21, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Daiichi Sankyo Company, Limited

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

August 31, 2020

First Posted Date ^ICMJE

September 4, 2020

Last Update Posted Date

February 21, 2023

Actual Study Start Date ^ICMJE

December 28, 2020

Estimated Primary Completion Date

February 26, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Occurrence of adverse events (AEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of adverse events (AEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 53 months ]
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0

Original Primary Outcome Measures ^ICMJE

Occurrence of adverse events (AEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 40 months ]
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 40 months ]
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of adverse events (AEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 40 months ]
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 40 months ]
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0

Change History

Current Secondary Outcome Measures ^ICMJE

Objective Response Rate (ORR)- Part 1 and Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.
Progression Free Survival (PFS)- Part 1 and Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
PFS is defined as time from the date of randomization until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.
Progression Free Survival 2 (PFS2)- Part 2 [ Time Frame: Assessed up to approximately 53 months ]
PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.
Duration of Response (DoR)- Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Overall Survival (OS)- Part 2 [ Time Frame: Until death, assessed up to approximately 53 months ]
OS is defined as time from the date of randomisation until the date of death due to any cause.
Serum Concentration of Trastuzumab Deruxtecan (T-DXd) [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Serum Concentration of Durvalumab [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of durvalumab concentration in serum at different time points after administration
Serum Concentration of Pertuzumab [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of pertuzumab concentration in serum at different time points after administration
Plasma Concentration of Paclitaxel [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of paclitaxel concentration in plasma at different time points after administration
Plasma Concentration of Tucatinib [ Time Frame: While on study drug up to study completion, approximately 53 months ]
Determination of tucatinib concentration in plasma at different time points after administration
Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 53 months ]
Percentage of patients who develop ADA for trastuzumab deruxtecan
Immunogenicity of Durvalumab [ Time Frame: Up to follow-up period, approximately 53 months ]
Percentage of patients who develop ADA for durvalumab
Immunogenicity of Pertuzumab [ Time Frame: Up to follow-up period, approximately 53 months ]
Percentage of patients who develop ADA for pertuzumab

Original Secondary Outcome Measures ^ICMJE

Objective Response Rate (ORR)- Part 2 [ Time Frame: Until progression, assessed up to approximately 40 months ]
ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.
Progression Free Survival (PFS)- Part 2 [ Time Frame: Until progression, assessed up to approximately 40 months ]
PFS is defined as time from the date of randomization until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.
Progression Free Survival 2 (PFS2)- Part 2 [ Time Frame: Assessed up to approximately 40 months ]
PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.
Duration of Response (DoR)- Part 2 [ Time Frame: Until progression, assessed up to approximately 40 months ]
DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Overall Survival (OS)- Part 2 [ Time Frame: Until death, assessed up to approximately 40 months ]
OS is defined as time from the date of randomisation until the date of death due to any cause.
Serum Concentration of Trastuzumab Deruxtecan (T-DXd) [ Time Frame: While on study drug up to study completion, approximately 40 months ]
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Serum Concentration of Durvalumab [ Time Frame: While on study drug up to study completion, approximately 40 months ]
Determination of durvalumab concentration in serum at different time points after administration
Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 40 months ]
Percentage of patients who develop ADA for trastuzumab deruxtecan
Immunogenicity of Durvalumab [ Time Frame: Up to follow-up period, approximately 40 months ]
Percentage of patients who develop ADA for durvalumab
Immunogenicity of Pertuzumab [ Time Frame: Up to follow-up period, approximately 40 months ]
Percentage of patients who develop ADA for pertuzumab

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer

Official Title ^ICMJE

A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)

Brief Summary

DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anti-cancer agents in patients with HER2-positive Metastatic Breast Cancer

Detailed Description

This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in Part 2.

The target population of interest in this study is patients with HER2-positive (as per ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

The study will consist of 2 phases: a dose escalation phase (Part 1) and a dose expansion phase (Part 2). Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later.Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Metastatic Breast Cancer

Intervention ^ICMJE

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion

Other Name: DS-8201a, T-DXd
Drug: Durvalumab
Durvalumab: administered as an IV infusion

Other Name: MEDI4736
Drug: Paclitaxel
Paclitaxel: administered as an IV infusion
Drug: Pertuzumab
Pertuzumab: administered as an IV infusion
Drug: Tucatinib
Tucatinib administered orally (tablet) twice daily

Other Name: ONT-380

Study Arms ^ICMJE

Experimental: Module 1- T-DXd and Durvalumab
T-DXd and Durvalumab
Interventions:
- Drug: Trastuzumab deruxtecan
- Drug: Durvalumab
Experimental: Module 2- T-DXd and Pertuzumab
T-DXd and Pertuzumab
Interventions:
- Drug: Trastuzumab deruxtecan
- Drug: Pertuzumab
Experimental: Module 3- T-DXd and Paclitaxel
T-DXd and Paclitaxel
Interventions:
- Drug: Trastuzumab deruxtecan
- Drug: Paclitaxel
Experimental: Module 4- T-DXd and Durvalumab and Paclitaxel
T-DXd and Durvalumab and Paclitaxel
Interventions:
- Drug: Trastuzumab deruxtecan
- Drug: Durvalumab
- Drug: Paclitaxel
Experimental: Module 0- T-DXd
T-DXd

Intervention: Drug: Trastuzumab deruxtecan
Experimental: Module 5 - T-DXd and Tucatanib
T-DXd and tucatinib
Interventions:
- Drug: Trastuzumab deruxtecan
- Drug: Tucatinib
Experimental: Module 6 - T-DXd and Tucatinib
T-DXd and tucatinib in patients with active brain metastases (Part 2 Only)
Interventions:
- Drug: Trastuzumab deruxtecan
- Drug: Tucatinib
Experimental: Module 7 - T-DXd
T-DXd monotherapy in patients with active brain metastases (Part 2 Only)

Intervention: Drug: Trastuzumab deruxtecan

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

245

Original Estimated Enrollment ^ICMJE

350

Estimated Study Completion Date ^ICMJE

December 30, 2025

Estimated Primary Completion Date

February 26, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key Inclusion Criteria:

Patients must be at least 18 years of age
Pathologically documented breast cancer that:
1. Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
2. HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting.
3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
Patient must have adequate tumor sample from the metastatic setting for biomarker assessment
ECOG Performance Status of 0 or 1
Part 1
1. Disease progression on or after the last systemic therapy prior to starting study treatment
2. At least 1 prior treatment line in metastatic setting required.
Part 2 (Modules 0 - 5)

a) No prior lines of therapy for advanced/MBC allowed
Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed

CNS Inclusion

Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.
Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy

Key Exclusion Criteria:

Uncontrolled or significant cardiovascular disease
Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
Lung-specific intercurrent clinically significant illnesses
Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
Spinal cord compression or a history of leptomeningeal carcinomatosis
Prior treatment with immune checkpoint inhibitors
Prior treatment with an ADC containing a topoisomerase I inhibitor
Prior treatment with tucatinib

CNS Exclusion

Modules 0 - 5: Has untreated brain metastasis
Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: AstraZeneca Clinical Study Information Center	1-877-240-9479	information.center@astrazeneca.com
Contact: AZ Breast Cancer Study Navigators	+1-877-400-4656	AstraZeneca@CareboxHealth.com

Listed Location Countries ^ICMJE

Australia, Brazil, Canada, France, Germany, India, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04538742

Other Study ID Numbers ^ICMJE

D967JC00001

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:	When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home