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

Metastatic Breast Cancer Clinical Trial

— DB-07  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04538742
• Other study ID #: D967JC00001
• Secondary ID: 2019-004531-22
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 28, 2020
• Est. completion date: July 2, 2025

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 244
• Est. completion date: July 2, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
• Durvalumab
Durvalumab: administered as an IV infusion
• Paclitaxel
Paclitaxel: administered as an IV infusion
• Pertuzumab
Pertuzumab: administered as an IV infusion
• Tucatinib
Tucatinib administered orally (tablet) twice daily

Locations

Country	Name	City	State
Australia	Research Site	Melbourne
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sorocaba
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Toronto
France	Research Site	Villejuif Cedex
Germany	Research Site	München
Germany	Research Site	Würzburg
India	Research Site	Delhi
India	Research Site	Gurgaon
India	Research Site	Madurai
India	Research Site	Mumbai
Italy	Research Site	Bologna
Italy	Research Site	Milan
Italy	Research Site	Napoli
Italy	Research Site	Rome
Korea, Republic of	Research Site	Busan-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Bydgoszcz
Poland	Research Site	Koszalin
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Sankt-Peterburg
Russian Federation	Research Site	Sankt-Peterburg
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Taiwan	Research Site	Hualien
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan City
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United Kingdom	Research Site	Buckhurst Hill
United States	Research Site	Columbus	Ohio
United States	Research Site	Commack	New York
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Harrison	New York
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Saint Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo Company, Limited

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of adverse events (AEs)- Part 1	Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 53 months
Primary	Occurrence of serious adverse events (SAEs)- Part 1	Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 53 months
Primary	Occurrence of adverse events (AEs)- Part 2	Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 53 months
Primary	Occurrence of serious adverse events (SAEs)- Part 2	Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 53 months
Secondary	Objective Response Rate (ORR)- Part 1 and Part 2	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.	Until progression, assessed up to approximately 53 months
Secondary	Progression Free Survival (PFS)- Part 1 and Part 2	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.	Until progression, assessed up to approximately 53 months
Secondary	Progression Free Survival 2 (PFS2)- Part 2	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.	Assessed up to approximately 53 months
Secondary	Duration of Response (DoR)- Part 2	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.	Until progression, assessed up to approximately 53 months
Secondary	Overall Survival (OS)- Part 2	OS is defined as time from the date of randomisation until the date of death due to any cause.	Until death, assessed up to approximately 53 months
Secondary	Serum Concentration of Trastuzumab Deruxtecan (T-DXd)	Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration	While on study drug up to study completion, approximately 53 months
Secondary	Serum Concentration of Durvalumab	Determination of durvalumab concentration in serum at different time points after administration	While on study drug up to study completion, approximately 53 months
Secondary	Serum Concentration of Pertuzumab	Determination of pertuzumab concentration in serum at different time points after administration	While on study drug up to study completion, approximately 53 months
Secondary	Plasma Concentration of Paclitaxel	Determination of paclitaxel concentration in plasma at different time points after administration	While on study drug up to study completion, approximately 53 months
Secondary	Plasma Concentration of Tucatinib	Determination of tucatinib concentration in plasma at different time points after administration	While on study drug up to study completion, approximately 53 months
Secondary	Immunogenicity of trastuzumab deruxtecan	Percentage of patients who develop ADA for trastuzumab deruxtecan	Up to follow-up period, approximately 53 months
Secondary	Immunogenicity of Durvalumab	Percentage of patients who develop ADA for durvalumab	Up to follow-up period, approximately 53 months
Secondary	Immunogenicity of Pertuzumab	Percentage of patients who develop ADA for pertuzumab	Up to follow-up period, approximately 53 months

External Links

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