A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)

Breast Cancer Clinical Trial

Official title:

A Phase 3 Open-label, Randomised Study of Datopotamab Deruxtecan (DatoDXd) With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Who Have Residual Invasive Disease in the Breast and/or Axillary Lymph Nodes at Surgical Resection Following Neoadjuvant Systemic Therapy (TROPION-Breast03)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05629585
• Other study ID #: D926XC00001
• Secondary ID: 2022-002680-30
• Status: Recruiting
• Phase: Phase 3
• Start date: November 28, 2022
• Est. completion date: March 27, 2030

Study information

• Verified date: June 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, randomized, open-label, 3-arm, multicenter, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with ICT in participants with stage I to III TNBC with residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.

Description:

The study will investigate the efficacy and safety of Dato-DXd with or without durvalumab when compared with ICT (capecitabine and/or pembrolizumab) in participants with stage I to III TNBC who have residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.

The primary objective of the study is to demonstrate superiority of Dato-DXd in combination with durvalumab relative to ICT by assessment of iDFS in participants with stage I to III TNBC with residual invasive disease at surgical resection following neoadjuvant therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1075
• Est. completion date: March 27, 2030
• Est. primary completion date: September 20, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Participant must be = 18 years at the time of screening.

2. Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.

3. Residual invasive disease in the breast and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy.

4. Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane with or without platinum chemotherapy, with or without pembrolizumab.

5. No evidence of locoregional or distant relapse.

6. Surgical removal of all clinically evident disease in the breast and lymph nodes.

7. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.

8. All participants must provide an FFPE tumour sample from residual invasive disease at surgery for tissue-based analysis.

9. No adjuvant systemic therapy.

10. Radiotherapy (if indicated) delivered before the start of study intervention.

11. If post-operative radiation therapy is given, an interval of no more than 6 weeks between the completion of radiation therapy and the date of randomisation (radiation therapy can be completed during screening period). If no post-operative radiation therapy is given, an interval of no more than 16 weeks between the date of breast surgery and the date of randomisation.

12. Has LVEF = 50% by either an ECHO or MUGA scan within 28 days before randomisation.

13. Eligible for one of the therapy options listed as investigator's choice per investigator assessment.

14. No known germline BRCA1 or BRCA2 pathogenic mutation.

15. Adequate bone marrow reserve and organ function within 7 days before randomisation.

Exclusion Criteria:

1. Stage IV (metastatic) TNBC.

2. History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery.

3. Severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, serious chronic gastrointestinal conditions associated with diarrhea chronic diverticulitis or previous complicated diverticulitis.

4. History of another primary malignancy except for adequately resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ disease (including ductal carcinoma in situ) that has undergone potentially curative therapy, or other solid malignancy treated with curative intent with no known active disease within 5 years before randomisation and of low potential risk for recurrence.

5. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade = 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).

6. Active or prior documented autoimmune or inflammatory disorders.

7. Clinically significant corneal disease.

8. Active or uncontrolled hepatitis B or C virus infection.

9. Known HIV infection that is not well controlled

10. Active tuberculosis infection.

11. Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening.

12. Uncontrolled or significant cardiac disease.

13. History of non-infectious ILD/pneumonitis including radiation, pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.

14. Has severe pulmonary function compromise.

15. Any known active liver disease.

16. Grade = 2 peripheral neuropathy of any aetiology.

17. Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab.

18. Current or prior use of immunosuppressive medication within 14 days prior to randomisation.

19. Participants with a known severe hypersensitivity to Dato-DXd or any of the excipients of these products including but not limited to polysorbate 80 or other monoclonal antibodies.

20. Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors.

21. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to randomisation, randomisation into a prior Dato-DXd, T-DXd, or durvalumab study regardless of treatment assignment.

22. Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Dato-DXd
Experimental drug. Provided in 100mg vials. IV infusion
• Durvalumab
Experimental drug. Provided in 50mg vials. IV infusion
• Capecitabine
Active Comparator. Tablet. Oral route of administration
• Pembrolizumab
Active Comparator. Provided in 100mg vials. IV infusion

Locations

Country	Name	City	State
Belgium	Research Site	Anderlecht
Belgium	Research Site	Brussel
Belgium	Research Site	Bruxelles
Belgium	Research Site	Charleroi
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Hasselt
Belgium	Research Site	Liège
Belgium	Research Site	Namur
Belgium	Research Site	Sint-Niklaas
Belgium	Research Site	Wilrijk
Brazil	Research Site	Brasilia
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Vitória
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Laval	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	North Vancouver	British Columbia
Canada	Research Site	Oakville	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinan
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	Shenzhen
China	Research Site	Shijiazhuang
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Zhengzhou
Denmark	Research Site	Aalborg
Denmark	Research Site	Copenhagen
Denmark	Research Site	Herlev
Denmark	Research Site	Herning
Denmark	Research Site	Næstved
Denmark	Research Site	Odense C
Denmark	Research Site	Sønderborg
Denmark	Research Site	Vejle
France	Research Site	Angers Cedex 02
France	Research Site	Bordeaux
France	Research Site	Dijon
France	Research Site	Epagny Metz-Tessy
France	Research Site	Lyon
France	Research Site	Montpellier
France	Research Site	Nimes
France	Research Site	Paris Cedex 05
France	Research Site	Poitiers
France	Research Site	Rennes
France	Research Site	Saint Herblain Cedex
France	Research Site	Vandoeuvre Les Nancy
France	Research Site	Villejuif Cedex
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Heilbronn
Germany	Research Site	Kiel
Germany	Research Site	Langen
Germany	Research Site	Leipzig
Germany	Research Site	Ludwigsburg
Germany	Research Site	Mönchengladbach
Germany	Research Site	München
Germany	Research Site	Paderborn
Germany	Research Site	Regensburg
Germany	Research Site	Stuttgart
Germany	Research Site	Troisdorf
Germany	Research Site	Tübingen
Germany	Research Site	Witten
Germany	Research Site	Wuppertal
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Patras
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Italy	Research Site	Bologna
Italy	Research Site	Brescia
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Livorno
Italy	Research Site	Meldola
Italy	Research Site	Messina
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Japan	Research Site	Akashi-shi
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka
Japan	Research Site	Fukushima-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Koto-ku
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-shi
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	Tsukuba
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seongnam-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
Puerto Rico	Research Site	San Juan
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Bilbao (Vizcaya)
Spain	Research Site	Elche(Alicante)
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Toledo
Spain	Research Site	Valencia
Sweden	Research Site	Göteborg
Sweden	Research Site	Jönköping
Sweden	Research Site	Malmö
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Sundsvall
Sweden	Research Site	Uppsala
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Taiwan	Research Site	Yung Kang City
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Derry
United Kingdom	Research Site	Derry
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Greater London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Surrey
United Kingdom	Research Site	Taunton
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Allentown	Pennsylvania
United States	Research Site	Altamonte Springs	Florida
United States	Research Site	Anchorage	Alaska
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Annapolis	Maryland
United States	Research Site	Arlington Heights	Illinois
United States	Research Site	Athens	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Beachwood	Ohio
United States	Research Site	Bedford	Texas
United States	Research Site	Beverly Hills	California
United States	Research Site	Billings	Montana
United States	Research Site	Boston	Massachusetts
United States	Research Site	Camden	New Jersey
United States	Research Site	Canton	Ohio
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbia	Maryland
United States	Research Site	Columbus	Ohio
United States	Research Site	Costa Mesa	California
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Decatur	Illinois
United States	Research Site	Denton	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Des Moines	Iowa
United States	Research Site	Detroit	Michigan
United States	Research Site	Duarte	California
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Edmonds	Washington
United States	Research Site	El Paso	Texas
United States	Research Site	Elizabethtown	Kentucky
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fountain Valley	California
United States	Research Site	Fullerton	California
United States	Research Site	Gainesville	Virginia
United States	Research Site	Gainesville	Virginia
United States	Research Site	Germantown	Tennessee
United States	Research Site	Gilbert	Arizona
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Harbor City	California
United States	Research Site	Harrisburg	Pennsylvania
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Hollywood	Florida
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Hot Springs National Park	Arkansas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Iowa City	Iowa
United States	Research Site	Irvine	California
United States	Research Site	Issaquah	Washington
United States	Research Site	Kansas City	Missouri
United States	Research Site	Kennewick	Washington
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Jolla	California
United States	Research Site	Laguna Hills	California
United States	Research Site	Lakewood	California
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Loma Linda	California
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Lubbock	Texas
United States	Research Site	Madison	Wisconsin
United States	Research Site	Marietta	Georgia
United States	Research Site	Maywood	Illinois
United States	Research Site	McAllen	Texas
United States	Research Site	Meadville	Pennsylvania
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami Beach	Florida
United States	Research Site	Midlothian	Virginia
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Mount Kisco	New York
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Albany	Indiana
United States	Research Site	New Haven	Connecticut
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Newport Beach	California
United States	Research Site	Newport Beach	California
United States	Research Site	Norfolk	Virginia
United States	Research Site	Oakland	California
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Orange	California
United States	Research Site	Orlando	Florida
United States	Research Site	Palm Bay	Florida
United States	Research Site	Park Ridge	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Providence	Rhode Island
United States	Research Site	Puyallup	Washington
United States	Research Site	Reno	Nevada
United States	Research Site	Ridgewood	New Jersey
United States	Research Site	Roanoke	Virginia
United States	Research Site	Rochester	New York
United States	Research Site	Roseville	California
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Francisco	California
United States	Research Site	Santa Clara	California
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Sleepy Hollow	New York
United States	Research Site	Spokane Valley	Washington
United States	Research Site	Springdale	Arkansas
United States	Research Site	Sunnyvale	California
United States	Research Site	Tallahassee	Florida
United States	Research Site	Tempe	Arizona
United States	Research Site	Torrance	California
United States	Research Site	Tucson	Arizona
United States	Research Site	Tucson	Arizona
United States	Research Site	Upland	California
United States	Research Site	Vallejo	California
United States	Research Site	Walnut Creek	California
United States	Research Site	Washington	District of Columbia
United States	Research Site	West Columbia	South Carolina
United States	Research Site	West Hollywood	California
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Westbury	New York
United States	Research Site	Westwood	Kansas
United States	Research Site	Whittier	California
United States	Research Site	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo, SWOG Clinical Trials Partnerships

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Puerto Rico,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT	iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause.; iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. 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 HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs ICT.	From randomisation to date of the event, up to 57 months from first subject in
Secondary	Distant disease-free survival (DDFS) for Dato-DXd + durvalumab vs ICT	DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause.; DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments.; The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd + durvalumab vs ICT.	From randomisation to date of the event, up to 57 months from first subject in
Secondary	DDFS for Dato-DXd vs ICT	DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd vs ICT.	From randomisation to date of the event, up to 57 months from first subject in
Secondary	DDFS for Dato-DXd + durvalumab vs Dato-DXd	DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd + durvalumab vs Dato-DXd.	From randomisation to date of the event, up 57 months from first subject in
Secondary	Overall Survival (OS) for Dato-DXd + durvalumab vs ICT	OS is defined as time from randomisation until 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 received another anticancer therapy. The measure of interest will be the HR (hazard ratio) of OS for Dato-DXd + durvalumab vs ICT.	From randomisation to date of death, due to any cause, up to 87 months from first subject in
Secondary	OS for Dato-DXd vs ICT	OS is defined as time from randomisation until date of death due to any cause. The measure of interest will be the HR (hazard ratio) of OS for Dato-DXd vs ICT.	From randomisation to date of death, due to any cause, up to 87 months from first subject in
Secondary	iDFS for Dato-DXd vs ICT	iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause.; iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. 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 HR (hazard ratio) of iDFS for Dato-DXd vs ICT.	From randomisation to date of the event, up to 57 months from first subject in
Secondary	iDFS for Dato-DXd + durvalumab vs Dato-DXd	iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs Dato-DXd.	From randomisation to date of the event, up to 57 months from first subject in
Secondary	Participant-reported physical function in participants treated with Dato-DXd with or without durvalumab compared with ICT	Time to Deterioration (TTD) and actual scores in physical function as measured by the PROMIS Physical Function Short Form 8c.TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold.; The analysis will include all dosed participants. The measure of interest is the HR (hazard ratio) of TTD and mean between-arm difference in physical function for Dato-DXd with or without durvalumab compared with ICT.	From randomisation to date of the deterioration, up to 36 months after randomisation
Secondary	Participant-reported in GHS/QoL in participants treated with Dato-DXd with or without durvalumab compared with ICT	Time to Deterioration (TTD) and actual scores in GHS/QoL as measured by the GHS/QoL scale from the EORTC IL172.; TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold.; The analysis will include all randomised participants. The measure of interest is the HR (hazard ratio) of TTD and mean between-arm difference in GHS/QoL for Dato-DXd with or without durvalumab compared with ICT.	From randomisation to date of the deterioration, up to 36 months after randomisation
Secondary	Participant-reported fatigue in participants treated with Dato-DXd with or without durvalumab compared with ICT	Proportion of participants experiencing different levels of fatigue at 3 months (13weeks), 6 months (26 weeks), and 12 months (52 weeks) as measured by PROMIS Fatigue Short Form 7a.; The analysis will include all dosed participants. The measure of interest will be the proportion of participants reporting different levels of fatigue.	From randomisation to 24 months after randomisation
Secondary	Pharmacokinetics of Dato-DXd	Concentration of Dato- DXd, total anti-TROP2 antibody, and MAAA-1181 in plasma.	Day 1 of cycles 1,2,4,6,8 (Each cycle is 21 days)
Secondary	Immunogenicity of Dato-DXd	Presence of ADAs for Dato-DXd (confirmatory results: positive or negative; titres).	Day 1 of cycles 1,2,4,6,8 (Each cycle is 21 days) and within 35 days of completion of or discontinuation of study intervention (at an average of 6 months following randomization)
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	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