Clinical trial NCT04538742: A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Breast Cancer
HER2-positive
Brain Metastases
Trastuzumab Deruxtecan
T-DXd
DS-8201a
DESTINY-Breast07
Anti-HER2 Antibody Drug Conjugate (ADC)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Company, Limited
First posted: 2020-09-04
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of adverse events (AEs)- Part 1
timeFrame: Up to follow-up period, approximately 53 months
measure: Occurrence of serious adverse events (SAEs)- Part 1
timeFrame: Up to follow-up period, approximately 53 months
measure: Occurrence of adverse events (AEs)- Part 2
timeFrame: Up to follow-up period, approximately 53 months
measure: Occurrence of serious adverse events (SAEs)- Part 2
timeFrame: Up to follow-up period, approximately 53 months
Secondary outcomes:
measure: Objective Response Rate (ORR)- Part 1 and Part 2
timeFrame: Until progression, assessed up to approximately 53 months
measure: Progression Free Survival (PFS)- Part 1 and Part 2
timeFrame: Until progression, assessed up to approximately 53 months
measure: Progression Free Survival 2 (PFS2)- Part 2
timeFrame: Assessed up to approximately 53 months
measure: Duration of Response (DoR)- Part 2
timeFrame: Until progression, assessed up to approximately 53 months
measure: Overall Survival (OS)- Part 2
timeFrame: Until death, assessed up to approximately 53 months
measure: Serum Concentration of Trastuzumab Deruxtecan (T-DXd)
timeFrame: While on study drug up to study completion, approximately 53 months
measure: Serum Concentration of Durvalumab
timeFrame: While on study drug up to study completion, approximately 53 months
measure: Serum Concentration of Pertuzumab
timeFrame: While on study drug up to study completion, approximately 53 months
measure: Plasma Concentration of Paclitaxel
timeFrame: While on study drug up to study completion, approximately 53 months
measure: Plasma Concentration of Tucatinib
timeFrame: While on study drug up to study completion, approximately 53 months
measure: Immunogenicity of trastuzumab deruxtecan
timeFrame: Up to follow-up period, approximately 53 months
measure: Immunogenicity of Durvalumab
timeFrame: Up to follow-up period, approximately 53 months
measure: Immunogenicity of Pertuzumab
timeFrame: Up to follow-up period, approximately 53 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Commack
country: United States
facility: Research Site
state: New York
city: Harrison
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Melbourne
country: Australia
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Natal
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sorocaba
country: Brazil
facility: Research Site
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: München
country: Germany
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city: Würzburg
country: Germany
facility: Research Site
city: Delhi
country: India
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Madurai
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Busan-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Koszalin
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Sankt-Peterburg
country: Russian Federation
facility: Research Site
city: Sankt-Peterburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Hualien
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Buckhurst Hill
country: United Kingdom
facility: Research Site
Study officials:
References: