Breast Cancer; HER2-positive; Metastatic Clinical Trial
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)
| Verified date | February 2024 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 1156 |
| Est. completion date | December 30, 2029 |
| Est. primary completion date | March 28, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 130 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Research Site | Buenos Aires | |
| Argentina | Research Site | Caba | |
| Argentina | Research Site | Caba | |
| Argentina | Research Site | Caba | |
| Argentina | Research Site | Capital Federal | |
| Argentina | Research Site | Cipolletti | |
| Argentina | Research Site | Ciudad de Buenos Aires | |
| Argentina | Research Site | La Plata | |
| Argentina | Research Site | Mar del Plata | |
| Argentina | Research Site | Rosario | |
| Argentina | Research Site | Rosario | |
| Argentina | Research Site | San Salvador de Jujuy | |
| Belgium | Research Site | Brussels | |
| Belgium | Research Site | Bruxelles | |
| Belgium | Research Site | Charleroi | |
| Belgium | Research Site | Edegem | |
| Belgium | Research Site | Gent | |
| Belgium | Research Site | Leuven | |
| Belgium | Research Site | Liège | |
| Belgium | Research Site | Namur | |
| Brazil | Research Site | Florianópolis | |
| Brazil | Research Site | Goiânia | |
| Brazil | Research Site | Londrina | |
| Brazil | Research Site | Natal | |
| Brazil | Research Site | Porto Alegre | |
| Brazil | Research Site | Ribeirão Preto | |
| Brazil | Research Site | São Paulo | |
| Brazil | Research Site | Sorocaba | |
| Brazil | Research Site | Vitoria | |
| Canada | Research Site | Barrie | Ontario |
| Canada | Research Site | Calgary | Alberta |
| Canada | Research Site | Halifax | Nova Scotia |
| Canada | Research Site | Kitchener | Ontario |
| Canada | Research Site | Montreal | Quebec |
| Canada | Research Site | Montreal | Quebec |
| Canada | Research Site | Montreal | Quebec |
| Canada | Research Site | Montreal | Quebec |
| Canada | Research Site | Newmarket | Ontario |
| Canada | Research Site | North York | Ontario |
| Canada | Research Site | Saskatoon | Saskatchewan |
| Canada | Research Site | Ste-Foy | Quebec |
| Canada | Research Site | Toronto | Ontario |
| China | Research Site | Beijing | |
| China | Research Site | Beijing | |
| China | Research Site | Beijing | |
| China | Research Site | Changchun | |
| China | Research Site | Changsha | |
| China | Research Site | Changsha | |
| China | Research Site | Chengdu | |
| China | Research Site | Chongqing | |
| China | Research Site | Chongqing | |
| China | Research Site | Dalian | |
| China | Research Site | Guangzhou | |
| China | Research Site | Guangzhou | |
| China | Research Site | Guangzhou | |
| China | Research Site | Hangzhou | |
| China | Research Site | Hangzhou | |
| China | Research Site | Harbin | |
| China | Research Site | Kunming | |
| China | Research Site | Nanchang | |
| China | Research Site | Nanjing | |
| China | Research Site | Nanjing | |
| China | Research Site | Nanning | |
| China | Research Site | Qingdao | |
| China | Research Site | Shanghai | |
| China | Research Site | Shanghai | |
| China | Research Site | Shenyang | |
| China | Research Site | Shenzhen | |
| China | Research Site | Tianjin | |
| China | Research Site | Wu Han | |
| China | Research Site | Wuhan | |
| China | Research Site | Wuhan | |
| China | Research Site | Xi'an | |
| China | Research Site | Xi'an | |
| China | Research Site | Yinchuan | |
| China | Research Site | Zhengzhou | |
| Denmark | Research Site | Copenhagen O | |
| Denmark | Research Site | Sønderborg | |
| Denmark | Research Site | Vejle | |
| France | Research Site | Avignon | |
| France | Research Site | Besancon | |
| France | Research Site | Bordeaux | |
| France | Research Site | Caen Cedex | |
| France | Research Site | Le Mans | |
| France | Research Site | Montpellier | |
| France | Research Site | Montpellier | |
| France | Research Site | Nice Cedex 2 | |
| France | Research Site | Paris | |
| France | Research Site | Pierre Benite Cedex | |
| France | Research Site | Rennes | |
| France | Research Site | Saint Cloud | |
| France | Research Site | Saint Herblain | |
| France | Research Site | Toulouse Cedex 9 | |
| France | Research Site | Vandoeuvre les Nancy | |
| Germany | Research Site | Berlin | |
| Germany | Research Site | Dresden | |
| Germany | Research Site | Erlangen | |
| Germany | Research Site | Essen | |
| Germany | Research Site | Frankfurt am Main | |
| Germany | Research Site | Freiburg | |
| Germany | Research Site | Hamburg | |
| Germany | Research Site | Heidelberg | |
| Germany | Research Site | Leipzig | |
| Germany | Research Site | Muenster | |
| Germany | Research Site | Paderborn | |
| Hungary | Research Site | Budapest | |
| Hungary | Research Site | Budapest | |
| Hungary | Research Site | Budapest | |
| Hungary | Research Site | Budapest | |
| Hungary | Research Site | Budapest | |
| Hungary | Research Site | Gyor | |
| Hungary | Research Site | Kecskemét | |
| Hungary | Research Site | Nyíregyháza | |
| Hungary | Research Site | Szolnok | |
| India | Research Site | Ahmedabad | |
| India | Research Site | Bangalore | |
| India | Research Site | Bengaluru | |
| India | Research Site | Calicut | |
| India | Research Site | Gurgaon | |
| India | Research Site | Mysuru | |
| India | Research Site | Nashik | |
| India | Research Site | Nashik | |
| India | Research Site | New Delhi | |
| India | Research Site | New Delhi | |
| Israel | Research Site | Haifa | |
| Israel | Research Site | Jerusalem | |
| Israel | Research Site | Petah Tikva | |
| Israel | Research Site | Ramat Gan | |
| Israel | Research Site | Tel-Aviv | |
| Italy | Research Site | Bergamo | |
| Italy | Research Site | Candiolo | |
| Italy | Research Site | Genova | |
| Italy | Research Site | Livorno | |
| Italy | Research Site | Milan | |
| Italy | Research Site | Napoli | |
| Italy | Research Site | Padova | |
| Italy | Research Site | Rozzano | |
| Italy | Research Site | Udine | |
| Japan | Research Site | Akashi-shi | |
| Japan | Research Site | Aomori-shi | |
| Japan | Research Site | Bunkyo-ku | |
| Japan | Research Site | Chiba-shi | |
| Japan | Research Site | Chuo-ku | |
| Japan | Research Site | Fukushima-shi | |
| Japan | Research Site | Hidaka-shi | |
| Japan | Research Site | Hiroshima-shi | |
| Japan | Research Site | Hiroshima-shi | |
| Japan | Research Site | Isehara-shi | |
| Japan | Research Site | Kagoshima-shi | |
| Japan | Research Site | Kawasaki-shi | |
| Japan | Research Site | Kobe-shi | |
| Japan | Research Site | Koto-ku | |
| Japan | Research Site | Kurume-shi | |
| Japan | Research Site | Kyoto-shi | |
| Japan | Research Site | Matsuyama-shi | |
| Japan | Research Site | Nagoya-shi | |
| Japan | Research Site | Nagoya-shi | |
| Japan | Research Site | Niigata-shi | |
| Japan | Research Site | Nishinomiya-shi | |
| Japan | Research Site | Okayama | |
| Japan | Research Site | Osaka-shi | |
| Japan | Research Site | Ota-shi | |
| Japan | Research Site | Sapporo-shi | |
| Japan | Research Site | Sendai-shi | |
| Japan | Research Site | Shinagawa-ku | |
| Japan | Research Site | Shinjuku-ku | |
| Japan | Research Site | Shinjuku-ku | |
| Japan | Research Site | Shizuoka | |
| Japan | Research Site | Tsu-shi | |
| Japan | Research Site | Yokohama-shi | |
| Korea, Republic of | Research Site | Cheonan-si | |
| Korea, Republic of | Research Site | Daegu | |
| Korea, Republic of | Research Site | Goyang-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 | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Mexico | Research Site | Alc. Cuauhtémoc | |
| Mexico | Research Site | Estado de México | |
| Mexico | Research Site | Guadalajara | |
| Mexico | Research Site | Metepec | |
| Mexico | Research Site | Nuevo Leon | |
| Mexico | Research Site | Veracruz | |
| Peru | Research Site | Arequipa | |
| Peru | Research Site | Lima | |
| Peru | Research Site | Lima | |
| Peru | Research Site | Lima | |
| Peru | Research Site | Lima | |
| Philippines | Research Site | Baguio City | |
| Philippines | Research Site | Cebu City | |
| Philippines | Research Site | Davao City | |
| Philippines | Research Site | Iloilo City | |
| Philippines | Research Site | Manila | |
| Philippines | Research Site | Quezon City | |
| Philippines | Research Site | San Juan | |
| Romania | Research Site | Bucharest | |
| Romania | Research Site | Floresti | |
| Romania | Research Site | Timisoara | |
| 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 | Saint Petersburg | |
| Russian Federation | Research Site | Yaroslavl | |
| Saudi Arabia | Research Site | Dammam | |
| Saudi Arabia | Research Site | Jeddah | |
| Saudi Arabia | Research Site | Jeddah | |
| Saudi Arabia | Research Site | Riyadh | |
| Saudi Arabia | Research Site | Riyadh | |
| Saudi Arabia | Research Site | Riyadh | |
| South Africa | Research Site | Cape Town | |
| South Africa | Research Site | Cape Town | |
| South Africa | Research Site | George | |
| South Africa | Research Site | Johannesburg | |
| South Africa | Research Site | Parktown | |
| South Africa | Research Site | Port Elizabeth | |
| South Africa | Research Site | Pretoria | |
| South Africa | Research Site | Rondebosch | |
| South Africa | Research Site | Soweto | |
| Spain | Research Site | Alicante | |
| Spain | Research Site | Barcelona | |
| Spain | Research Site | Barcelona | |
| Spain | Research Site | Barcelona | |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Majadahonda | |
| Spain | Research Site | Sevilla | |
| Sweden | Research Site | Göteborg | |
| Sweden | Research Site | Örebro | |
| Sweden | Research Site | Stockholm | |
| Sweden | Research Site | Uppsala | |
| Sweden | Research Site | Växjö | |
| Taiwan | Research Site | Taichung | |
| Taiwan | Research Site | Tainan | |
| Taiwan | Research Site | Taipei | |
| Taiwan | Research Site | Taipei | |
| Taiwan | Research Site | Taipei | |
| Taiwan | Research Site | Taipei | |
| Taiwan | Research Site | Taoyuan | |
| Turkey | Research Site | Adana | |
| Turkey | Research Site | Ankara | |
| Turkey | Research Site | Ankara | |
| Turkey | Research Site | Karsiyaka | |
| Turkey | Research Site | Malatya | |
| Turkey | Research Site | Samsun | |
| United Kingdom | Research Site | Buckhurst Hill | |
| United Kingdom | Research Site | Edinburgh | |
| United Kingdom | Research Site | Guildford | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | Manchester | |
| United Kingdom | Research Site | Swansea | |
| United Kingdom | Research Site | Taunton | |
| United States | Research Site | Atlanta | Georgia |
| United States | Research Site | Boston | Massachusetts |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Denton | Texas |
| United States | Research Site | Detroit | Michigan |
| United States | Research Site | Germantown | Tennessee |
| United States | Research Site | Glendale | California |
| United States | Research Site | Glendale | California |
| United States | Research Site | Houston | Texas |
| United States | Research Site | Jackson | Mississippi |
| United States | Research Site | Las Vegas | Nevada |
| United States | Research Site | Longmont | Colorado |
| United States | Research Site | Louisville | Kentucky |
| United States | Research Site | Miami | Florida |
| United States | Research Site | New York | New York |
| United States | Research Site | Norfolk | Virginia |
| United States | Research Site | Palm Bay | Florida |
| United States | Research Site | Plantation | Florida |
| United States | Research Site | Roanoke | Virginia |
| United States | Research Site | San Antonio | Texas |
| United States | Research Site | Shenandoah | Texas |
| United States | Research Site | Shirley | New York |
| United States | Research Site | Silver Spring | Maryland |
| United States | Research Site | Springdale | Arkansas |
| United States | Research Site | Summit | New Jersey |
| United States | Research Site | Tacoma | Washington |
| United States | Research Site | Tucson | Arizona |
| United States | Research Site | Tyler | Texas |
| United States | Research Site | York | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca | Daiichi Sankyo |
United States, Argentina, Belgium, Brazil, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Peru, Philippines, Romania, Russian Federation, Saudi Arabia, South Africa, Spain, Sweden, Taiwan, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment | Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause. | Until progression or death, assessed up to approximately 60 months | |
| Secondary | Progression Free Survival (PFS) by Investigator assessment | Defined as time from date of randomisation until the date of objective radiological disease progression according to Investigator using RECIST 1.1 or death by any cause. | Until progression or death, assessed up to approximately 60 months | |
| Secondary | Overall Survival (OS) | OS is defined as the time from randomisation until the date of death due to any cause. | Until death, assessed up to approximately 104 months | |
| Secondary | Objective Response Rate (ORR) by BICR and Investigator assessment | ORR is defined as The proportion of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1. | Until progression or death (in the absence of progression), assessed up to approximately 60 months | |
| Secondary | Duration of Response (DoR) by BICR and Investigator Assessment | DoR is defined as the time from date of first detection of objective response until the date of objective radiological disease progression according to BICR and investigator assessment using RECIST 1.1 or death in the absence of progression. | Until progression or death (in the absence of progression), assessed up to approximately 60 months | |
| Secondary | Time to second progression or death (PFS2) by Investigator assessment | PFS2 is defined as the time from randomisation until the date of tumor progression on next-line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy after the first progression) or death from any cause; second progression will be defined according to local standard clinical practice. | Assessed up to approximately 104 months | |
| Secondary | 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'. | Pain progression: Time to sustained deterioration of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Pain Scale. Scores range from 0-100 based on 2 items with responses ranging from 1-4. A lower score would mean better outcome. | Assessed up to approximately 60 months | |
| Secondary | To assess patient-reported treatment tolerability | Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, general cancer module (EORTC QLQ-C30), score of 1-4. A lower score would mean better outcome. | Assessed up to approximately 60 months | |
| Secondary | To assess patient-reported treatment tolerability | Proportion of patients reporting different levels of overall tolerability as measured by the Patient Global Impression of Treatment Tolerability (PGI-TT), score of 0-4. A lower score would mean a better outcome. | Assessed up to approximately 60 months | |
| Secondary | To assess patient-reported treatment tolerability | Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, breast cancer module (EORTC QLQ-BR45), score of 1-4. A lower score would mean better outcome. | Assessed up to approximately 60 months | |
| Secondary | To assess patient-reported treatment tolerability | Proportion of participants experiencing treatment related symptoms as measured by selected items from the Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events (PRO-CTCAE). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). A lower score would mean a better outcome. | Assessed up to approximately 60 months | |
| Secondary | To assess patient-reported treatment tolerability | The proportion of participants with maintained or improved physical function while on treatment, based on the EORTC QLQ-C30 Physical Functioning scale. Scores range from 0-100, based on 5 items with responses ranging from 1-4. A higher score would mean a better outcome. | Assessed up to approximately 60 months | |
| Secondary | Serum concentration of trastuzumab deruxtecan and pertuzumab | Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum. | Up to Cycle 6, approximately Week 18; each cycle is 21 days | |
| Secondary | Immunogenicity of trastuzumab deruxtecan. | Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan. | Up to follow-up period, approximately 60 months | |
| Secondary | Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab | Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm | Assessed up to approximately 60 months |