Clinical trial NCT04784715: Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)
Official title: Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer; HER2-positive; Metastatic
Keywords: Breast Neoplasms; Breast Diseases; Trastuzumab; Antineoplastic Agents, Phytogenic; Anti-drug conjugate; Molecular Mechanisms of Pharmacological Action;
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2021-03-05
Enrollment: 1157
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study will consist of three arms:

Arm A - trastuzumab deruxtecan with pertuzumab-matching placebo Arm B - trastuzumab deruxtecan with pertuzumab Arm C - standard of care (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab)
Primary purpose: TREATMENT

Brief summary: The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.

Detailed description: Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer.

The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Eligibility criteria: Key Inclusion Criteria:

* Patients must be ≥18 years of age
* Pathologically documented breast cancer that:

  1. is advanced or metastatic
  2. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
  3. is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting
* No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if \> 6 months from treatment to metastatic diagnosis.
* Has protocol-defined adequate organ and bone marrow function
* ECOG performance status 0 or 1

Key Exclusion Criteria:

* Ineligible for any of the agents on the study.
* Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results
* Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
* Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
* Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment

Primary outcomes:
measure: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment
timeFrame: Until progression or death, assessed up to approximately 60 months
Secondary outcomes:
measure: Progression Free Survival (PFS) by Investigator assessment
timeFrame: Until progression or death, assessed up to approximately 60 months
measure: Overall Survival (OS)
timeFrame: Until death, assessed up to approximately 104 months
measure: Objective Response Rate (ORR) by BICR and Investigator assessment
timeFrame: Until progression or death (in the absence of progression), assessed up to approximately 60 months
measure: Duration of Response (DoR) by BICR and Investigator Assessment
timeFrame: Until progression or death (in the absence of progression), assessed up to approximately 60 months
measure: Time to second progression or death (PFS2) by Investigator assessment
timeFrame: Assessed up to approximately 104 months
measure: To assess the effect of T-DXd ± pertuzumab relative to THP in terms of patient-reported pain in participants with HER2 positive, first-line mBC'.
timeFrame: Assessed up to approximately 60 months
measure: To assess patient-reported treatment tolerability
timeFrame: Assessed up to approximately 60 months
measure: To assess patient-reported treatment tolerability
timeFrame: Assessed up to approximately 60 months
measure: To assess patient-reported treatment tolerability
timeFrame: Assessed up to approximately 60 months
measure: To assess patient-reported treatment tolerability
timeFrame: Assessed up to approximately 60 months
measure: To assess patient-reported treatment tolerability
timeFrame: Assessed up to approximately 60 months
measure: Serum concentration of trastuzumab deruxtecan and pertuzumab
timeFrame: Up to Cycle 6, approximately Week 18; each cycle is 21 days
measure: Immunogenicity of trastuzumab deruxtecan.
timeFrame: Up to follow-up period, approximately 60 months
measure: Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab
timeFrame: Assessed up to approximately 60 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Springdale
country: United States
facility: Research Site
state: Arkansas
city: Glendale
country: United States
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state: California
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state: California
city: Longmont
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state: Colorado
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state: Michigan
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state: New Jersey
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city: Denton
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city: Houston
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state: Virginia
city: Roanoke
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state: Washington
city: Buenos Aires
country: Argentina
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country: Argentina
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country: Argentina
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city: Capital Federal
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city: Cipolletti
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city: Bruxelles
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city: Charleroi
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city: Edegem
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city: Gent
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city: Liège
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state: Alberta
city: Halifax
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state: Nova Scotia
city: Barrie
country: Canada
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city: Kitchener
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city: Newmarket
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city: North York
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city: Toronto
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city: Montreal
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city: Montreal
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city: Montreal
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city: Ste-Foy
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city: Saskatoon
country: Canada
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state: Saskatchewan
city: Beijing
country: China
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city: Beijing
country: China
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country: China
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city: Changchun
country: China
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city: Changsha
country: China
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country: China
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city: Chengdu
country: China
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city: Chongqing
country: China
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country: China
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city: Dalian
country: China
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city: Guangzhou
country: China
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city: Guangzhou
country: China
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country: China
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city: Hangzhou
country: China
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city: Hangzhou
country: China
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city: Harbin
country: China
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city: Kunming
country: China
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city: Nanchang
country: China
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city: Nanjing
country: China
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city: Nanjing
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: Shenzhen
country: China
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city: Tianjin
country: China
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city: Wu Han
country: China
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city: Wuhan
country: China
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city: Wuhan
country: China
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city: Xi'an
country: China
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city: Xi'an
country: China
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city: Yinchuan
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: Copenhagen O
country: Denmark
facility: Research Site
city: Sønderborg
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Avignon
country: France
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city: Besancon
country: France
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city: Bordeaux
country: France
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city: Caen Cedex
country: France
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city: Le Mans
country: France
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city: Montpellier
country: France
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city: Montpellier
country: France
facility: Research Site
city: Nice Cedex 2
country: France
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city: Paris
country: France
facility: Research Site
city: Pierre Benite Cedex
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Saint Cloud
country: France
facility: Research Site
city: Saint Herblain
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
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city: Freiburg
country: Germany
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city: Hamburg
country: Germany
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city: Heidelberg
country: Germany
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city: Leipzig
country: Germany
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city: Muenster
country: Germany
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city: Paderborn
country: Germany
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Győr
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city: Kecskemét
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city: Nyíregyháza
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city: Szolnok
country: Hungary
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city: Ahmedabad
country: India
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city: Bangalore
country: India
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city: Bengaluru
country: India
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city: Calicut
country: India
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city: Gurgaon
country: India
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city: Mysuru
country: India
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city: Nashik
country: India
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city: Nashik
country: India
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city: New Delhi
country: India
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city: New Delhi
country: India
facility: Research Site
city: Haifa
country: Israel
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city: Jerusalem
country: Israel
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city: Petah Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Candiolo
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Livorno
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Udine
country: Italy
facility: Research Site
city: Akashi-shi
country: Japan
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city: Aomori-shi
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
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city: Chiba-shi
country: Japan
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city: Chuo-ku
country: Japan
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city: Fukushima-shi
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
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city: Isehara-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
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city: Kurume-shi
country: Japan
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city: Kyoto-shi
country: Japan
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city: Matsuyama-shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Niigata-shi
country: Japan
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city: Nishinomiya-shi
country: Japan
facility: Research Site
city: Okayama
country: Japan
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city: Osaka-shi
country: Japan
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city: Ota-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
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city: Sendai-shi
country: Japan
facility: Research Site
city: Shinagawa-ku
country: Japan
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city: Shinjuku-ku
country: Japan
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city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shizuoka
country: Japan
facility: Research Site
city: Tsu-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Cheonan-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Goyang-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: 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: Alc. Cuauhtémoc
country: Mexico
facility: Research Site
city: Estado de México
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Metepec
country: Mexico
facility: Research Site
city: Nuevo Leon
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Arequipa
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
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city: Lima
country: Peru
facility: Research Site
city: Baguio City
country: Philippines
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city: Cebu City
country: Philippines
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city: Davao City
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
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city: Manila
country: Philippines
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city: Quezon City
country: Philippines
facility: Research Site
city: San Juan
country: Philippines
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city: Bucharest
country: Romania
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city: Floresti
country: Romania
facility: Research Site
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Dammam
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: George
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
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city: Johannesburg
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
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city: Pretoria
country: South Africa
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city: Rondebosch
country: South Africa
facility: Research Site
city: Soweto
country: South Africa
facility: Research Site
city: Alicante
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
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city: Sevilla
country: Spain
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city: Göteborg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Växjö
country: Sweden
facility: Research Site
city: Örebro
country: Sweden
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
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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
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Buckhurst Hill
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
Study officials:
References: