A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients With Previously Untreated Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer (D926QC00001; TROPION-Breast04)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06112379
• Other study ID #: D926QC00001
• Status: Recruiting
• Phase: Phase 3
• Start date: November 14, 2023
• Est. completion date: August 28, 2030

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer.

Description:

The primary objectives of the study are to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor low/HER2-negative breast cancer, by central assessment of pCR and/or to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer, by investigator assessment of EFS

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1728
• Est. completion date: August 28, 2030
• Est. primary completion date: March 29, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must be = 18 years, at the time of signing the ICF.
• Histologically confirmed Stage II or III unilateral or bilateral primary invasive TNBC or hormone receptor-low/HER2-negative breast cancer
• ECOG PS of 0 or 1
• Provision of acceptable tumor sample
• Adequate bone marrow reserve and organ function
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion criteria:

• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before randomization and of low potential risk for recurrence.
• Evidence of distant disease.
• Clinically significant corneal disease.
• Has active or uncontrolled hepatitis B or C virus infection.
• Known HIV infection that is not well controlled.
• Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections; or inability to rule out infections.
• Known to have active tuberculosis infection
• Resting ECG with clinically significant abnormal findings.
• Uncontrolled or significant cardiac disease.
• History of non-infectious ILD/pneumonitis
• Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for TNBC or hormone receptor-low/HER2-negative breast cancer
• For females only: is pregnant (confirmed with positive serum pregnancy test) or breastfeeding, or planning to become pregnant.
• Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of study intervention, or as dictated by local PI for SoC if longer.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Dato-DXd
Experimental drug IV infusion
• Durvalumab
Experimental drug IV Infusion
• Pembrolizumab
IV Infusion Active comparator
• Doxorubicin
IV infusion Experimental/Active Comparator
• Epirubicin
IV Infusion Experimental/Active Comparator
• Cyclophosphamide
IV infusion Experimental/Active Comparator
• Paclitaxel
IV infusion Experimental/Active Comparator
• Carboplatin
IV infusion Experimental/Active Comparator
• Capecitabine
Tablet Oral route of administration Experimental/Active Comparator
• Olaparib
Tablet Oral route of administration Experimental/Active Comparator

Locations

Country	Name	City	State
Australia	Research Site	Darlinghurst
Australia	Research Site	East Melbourne
Australia	Research Site	Heidelberg
Australia	Research Site	Herston
Australia	Research Site	Nedlands
Australia	Research Site	Waratah
Austria	Research Site	Feldkirch
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Belgium	Research Site	Brasschaat
Belgium	Research Site	Charleroi
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Libramont-Chevigny
Belgium	Research Site	Wilrijk
Brazil	Research Site	Brasilia
Brazil	Research Site	Curitiba
Brazil	Research Site	Fortaleza
Brazil	Research Site	Londrina
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Santo Andre
Brazil	Research Site	São Paulo
Brazil	Research Site	Taubaté
Brazil	Research Site	Vitória
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Shumen
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Vratza
Canada	Research Site	Abbotsford	British Columbia
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Levis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Ottawa
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	St-Jerome	Quebec
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Kunming
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Shijiazhuang
China	Research Site	Suining
China	Research Site	Suzhou
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xintai
France	Research Site	Avignon
France	Research Site	Bayonne
France	Research Site	Caen Cedex 5
France	Research Site	Clermont Ferrand
France	Research Site	Limoges
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Reims Cedex
France	Research Site	Saint Herblain
France	Research Site	Toulouse
France	Research Site	Vandoeuvre les Nancy
France	Research Site	Villejuif Cedex
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Dessau-Roßlau
Germany	Research Site	Dresden
Germany	Research Site	Erlangen
Germany	Research Site	Essen
Germany	Research Site	Esslingen am Neckar
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Freiburg
Germany	Research Site	Freiburg
Germany	Research Site	Hannover
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Kiel
Germany	Research Site	Mainz
Germany	Research Site	Mannheim
Germany	Research Site	München
Germany	Research Site	Münster
Germany	Research Site	Trier
Germany	Research Site	Ulm
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Kwai Chung
Hungary	Research Site	Budapest
Hungary	Research Site	Kecskemét
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Salgótarján
Hungary	Research Site	Szekszárd
India	Research Site	Bengaluru
India	Research Site	Dehradun
India	Research Site	Delhi
India	Research Site	Delhi
India	Research Site	Kolkata
India	Research Site	Kolkata
India	Research Site	Marg Jaipur
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	Puducherry
India	Research Site	Thiruvananthapuram
India	Research Site	Vadodara
Italy	Research Site	Empoli
Italy	Research Site	Lucca
Italy	Research Site	Macerata
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Torino
Italy	Research Site	Tricase
Italy	Research Site	Udine
Japan	Research Site	Akashi-shi
Japan	Research Site	Akita-shi
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukushima-shi
Japan	Research Site	Gifu-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama
Japan	Research Site	Osaka-shi
Japan	Research Site	Sapporo-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	Sunto-gun
Japan	Research Site	Tokyo
Japan	Research Site	Tsu-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seongnam
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
Malaysia	Research Site	George Town
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Selangor
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Lódz
Poland	Research Site	Tomaszów Mazowiecki
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Singapore	Research Site	Singapore
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Granada
Spain	Research Site	Hospitalet deLlobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
Spain	Research Site	Zaragoza
Switzerland	Research Site	Baden
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Frauenfeld
Switzerland	Research Site	Rennaz
Taiwan	Research Site	Changhua
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Dusit
Thailand	Research Site	Muang
Thailand	Research Site	Songkhla
Turkey	Research Site	Adapazari
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Kayseri
Turkey	Research Site	Samsun
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Lancaster
United Kingdom	Research Site	London
United Kingdom	Research Site	Northampton
United Kingdom	Research Site	Oxford
United States	Research Site	Annapolis	Maryland
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bridgeport	Connecticut
United States	Research Site	Burnsville	Minnesota
United States	Research Site	Camden	New Jersey
United States	Research Site	Canton	Ohio
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Columbia	Missouri
United States	Research Site	Commack	New York
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Daphne	Alabama
United States	Research Site	Des Moines	Iowa
United States	Research Site	Detroit	Michigan
United States	Research Site	Durham	North Carolina
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Edgewood	Kentucky
United States	Research Site	El Paso	Texas
United States	Research Site	Eugene	Oregon
United States	Research Site	Falls Church	Virginia
United States	Research Site	Flower Mound	Texas
United States	Research Site	Fort Collins	Colorado
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Goodyear	Arizona
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Henderson	Nevada
United States	Research Site	Horsham	Pennsylvania
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	Longmont	Colorado
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Norfolk	Virginia
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Jefferson Station	New York
United States	Research Site	Port Saint Lucie	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Providence	Rhode Island
United States	Research Site	Richmond	Virginia
United States	Research Site	Roanoke	Virginia
United States	Research Site	Rogers	Arkansas
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Barbara	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Sylmar	California
United States	Research Site	Tacoma	Washington
United States	Research Site	Tallahassee	Florida
United States	Research Site	Torrance	California
United States	Research Site	Traverse City	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Van Nuys	California
United States	Research Site	Webster	Texas
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Winchester	Virginia
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh city
Vietnam	Research Site	Ho Chi Minh city
Vietnam	Research Site	Vinh

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  France,  Germany,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Singapore,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response (pCR) in the experimental vs control arms	pCR rate is defined as the proportion of participants who have no evidence by haematoxylin and eosin staining of residual invasive disease at the time of definitive surgery in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by blinded central evaluation.; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.; The measure of interest will be the difference between the pCR rates.	At the time of definitive surgery
Primary	Event-free survival (EFS) in the experimental vs control arms	EFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: disease progression precluding surgery, disease recurrence (local, regional, distant, or contralateral), second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death by any cause (in the absence of recurrence).; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.; The measure of interest will be the Hazard Ratio of EFS.	Date of randomization to date of the EFS event, up to 68 months after the first subject randomized
Secondary	Overall Survival (OS) in the experimental vs control arms	OS is defined as the time from the date of randomisation until the date of death due to any cause.; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.; The measure of interest will be the Hazard Ratio of OS.	Date of randomization to date of death due to any cause, up to 82 months after the first subject randomized
Secondary	Distant disease-free survival (DDFS) in the experimental vs control arms	DDFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: distant metastasis, occurrence of second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death by any cause (in the absence of recurrence).; The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.; The measure of interest will be the Hazard Ratio of DDFS.	Date of randomization to date of the DDFS event, up to 68 months after the first subject randomized
Secondary	Participant-reported breast and arm symptoms in the experimental vs. control arms	Breast and arm symptoms measured by the EORTC IL116. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.; The measure of interest is the mean between-arm difference in breast and arm symptom scores.	From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first.
Secondary	Participant-reported physical function in the experimental vs. control arms	Physical function measured by the PROMIS Physical Function Short Form 8c. The analysis will include all dosed participants. The measure of interest is the mean between-arm difference in physical function scores.	From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
Secondary	Participant-reported fatigue in the experimental vs. control arms	Fatigue measured by the PROMIS Fatigue Short Form 7a. The analysis will include all dosed participants. The measure of interest will be the difference on the proportions of participants reporting different levels of fatigue and mean between-arm difference in the fatigue scores.	From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
Secondary	Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control arms	Global health status/Quality of life measured by EORTC IL172. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.; The measure of interest is the mean between-arm difference in GHS/QoL scores.	From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
Secondary	Pharmacokinetics of Dato-DXd (in combination with durvalumab)	Plasma concentrations of Dato-DXd (ug/ml )	Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Secondary	Pharmacokinetics of Dato-DXd (in combination with durvalumab)	Plasma concentrations of total anti-TROP2 antibody (ug/ml )	Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Secondary	Pharmacokinetics of Dato-DXd (in combination with durvalumab)	Plasma concentrations of DXd (MAAA-1181a) (ng/ml)	Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Secondary	Immunogenicity of Dato-DXd (in combination with durvalumab)	Presence of antidrug antibodies (ADAs) for Dato-DXd (confirmatory results: positive or negative, titres).	Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
Secondary	Safety of Dato-DXd (in combination with durvalumab)	Safety and tolerability will be evaluated in terms of AEs graded by CTCAE version 5.0	Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely