A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast05)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06103864
• Other study ID #: D7630C00001
• Status: Recruiting
• Phase: Phase 3
• Start date: November 23, 2023
• Est. completion date: April 23, 2029

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, randomised, open-label, 3-arm, multicentre, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with investigator's choice chemotherapy in combination with pembrolizumab in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.

Description:

The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.

The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI > 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs. no).

This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 625
• Est. completion date: April 23, 2029
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria

• Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines.

• ECOG PS 0 or 1.

• All participants must provide a FFPE metastatic or locally recurrent inoperable tumour sample.

• PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS = 10) from a sponsor designated central laboratory.

• No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.

• Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and =6 months have elapsed between completion of treatment with curative intent and the first documented recurrence.

• Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin).

• Measurable disease as per RECIST 1.1.

• Adequate bone marrow reserve and organ function.

• Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception.

Key Exclusion Criteria

• As judged by investigator, severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, significant cardiac or psychological conditions.

• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before Cycle 1 Day 1 and of low potential risk for recurrence.

• Neoplastic spinal cord compression or active brain metastases, leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis.

• Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.

• Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.

• Active or uncontrolled hepatitis B or C virus infection.

• Known HIV infection that is not well controlled.

• Uncontrolled or significant cardiac disease.

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

• Severe pulmonary function compromise.

• Clinically significant corneal disease.

• Active or prior documented autoimmune or inflammatory disorders.

• Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy.

• Any concurrent anti-cancer treatment.

• Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd.

• 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
Provided in 100mg vials. IV infusion. Experimental drug.
• Durvalumab
Provided in 500mg vials. IV infusion. Experimental drug.
• Paclitaxel
IV infusion. Active comparator.
• Nab-paclitaxel
IV infusion. Active comparator.
• Gemcitabine
IV infusion. Active comparator.
• Carboplatin
IV infusion. Active comparator.
• Pembrolizumab
IV infusion. Active comparator.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autonoma Bs As
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	San Nicolas de Los Arroyos
Australia	Research Site	Camperdown
Australia	Research Site	Darlinghurst
Australia	Research Site	Heidelberg
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	Waratah
Brazil	Research Site	Barretos
Brazil	Research Site	Curitiba
Brazil	Research Site	Florianópolis
Brazil	Research Site	Goiânia
Brazil	Research Site	Itajai
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Teresina
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montréal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Regina	Saskatchewan
Canada	Research Site	Saskatoon	Saskatchewan
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	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	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Ji Nan
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Shandong
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Xintai
China	Research Site	Xuzhou
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
France	Research Site	Lille
France	Research Site	Lyon
France	Research Site	Paris
France	Research Site	Saint Herblain Cedex
France	Research Site	Toulouse Cedex 9
Germany	Research Site	Düsseldorf
Germany	Research Site	Essen
Germany	Research Site	Georgsmarienhütte
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Heilbronn
Germany	Research Site	Leipzig
India	Research Site	Calicut
India	Research Site	Kochi
India	Research Site	Kolkata
India	Research Site	Marg Jaipur
India	Research Site	Mohali
India	Research Site	Mysuru
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Pondicherry
India	Research Site	Surat
India	Research Site	Vadodara
India	Research Site	Vishakapatnam
Italy	Research Site	Empoli
Italy	Research Site	Milan
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Japan	Research Site	Akashi-shi
Japan	Research Site	Bunkyo-ku
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	Hiroshima-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kamogawa-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kitaadachi-gun
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	Niigata-shi
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-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	Tsu-shi
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	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	CD Mexico
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	Mexico City
Mexico	Research Site	Tuxtla Gutierrez
Philippines	Research Site	Bacolod
Philippines	Research Site	Cebu City
Philippines	Research Site	Manila
Philippines	Research Site	Muntinlupa City
Philippines	Research Site	Quezon City
Philippines	Research Site	San Juan
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Konin
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Legnica
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Przemysl
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
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	Pamplona
Spain	Research Site	Santander
Taiwan	Research Site	Hsinchu
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	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Dusit
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Songkhla
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Besevler Ankara
Turkey	Research Site	Izmir
Turkey	Research Site	Küçükçekmece
Turkey	Research Site	Samsun
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Chelsea
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Surrey
United Kingdom	Research Site	Sutton
United States	Research Site	Albany	New York
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	Maryland
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	Decatur	Illinois
United States	Research Site	Des Moines	Iowa
United States	Research Site	Detroit	Michigan
United States	Research Site	Duarte	California
United States	Research Site	El Paso	Texas
United States	Research Site	Elmhurst	Illinois
United States	Research Site	Flower Mound	Texas
United States	Research Site	Fort Worth	Texas
United States	Research Site	Glendale	California
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Hattiesburg	Mississippi
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kingwood	Texas
United States	Research Site	Lexington	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	McKinney	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Midlothian	Virginia
United States	Research Site	Naperville	Illinois
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 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	Providence	Rhode Island
United States	Research Site	Roanoke	Virginia
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	Santa Rosa	California
United States	Research Site	Springdale	Arkansas
United States	Research Site	Stony Brook	New York
United States	Research Site	Sugar Land	Texas
United States	Research Site	Tacoma	Washington
United States	Research Site	Worcester	Massachusetts
United States	Research Site	York	Pennsylvania
Vietnam	Research Site	Hanoi
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,  Argentina,  Australia,  Brazil,  Canada,  China,  France,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Singapore,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1 progression.; However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits.; The measure of interest is the HR of PFS.	From randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (anticipated to be up to 33 months).
Secondary	Overall Survival (OS)	OS is defined as the time from randomisation until the date of death due to any cause.	From randomisation until the date of death due to any cause (anticipated to be up to 64 months).
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a CR or PR, as determined by the BICR/investigator assessment, per RECIST 1.1.	From randomisation up until progression (anticipated to be up to 33 months).
Secondary	Duration of Response (DoR)	DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause.	From the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause (anticipated to be up to 33 months).
Secondary	Progression-Free Survival (PFS) by Investigator assessment	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause.	From randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 33 months).
Secondary	Clinical Benefit Rate (CBR) at 24 weeks	CBR at 24 weeks is defined as the percentage of participants who have a CR or PR or who have SD, per RECIST 1.1, as assessed by BICR/per investigator assessment and derived from the raw tumour data for at least 23 weeks after randomisation.	From randomisation up until progression, or the last evaluable assessment in the absence of progression (anticipated to be up to 33 months).
Secondary	Time to deterioration (TTD) in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab	TTD in breast symptoms and arm symptoms as measured by the arm symptoms scale from EORTC IL116 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.	From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).
Secondary	Time to deterioration (TTD) in pain in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab	TTD in pain as measured by the EORTC IL199.	Time from the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).
Secondary	Time to deterioration (TTD) in physical functioning in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab	TTD in physical function as measured by the PROMIS Short Form v2.0 - Physical Function 8c.	From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).
Secondary	Time to deterioration (TTD) in GHS/QoL in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab	TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172.	From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression).
Secondary	Time to First Subsequent Therapy (TFST)	TFST is defined as the time from randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause.	From randomisation until the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause (anticipated to be up to 64 months).
Secondary	Time to Second Subsequent Therapy (TSST)	TSST is defined as the time from randomisation until the start date of the second subsequent anticancer therapy after discontinuation of first subsequent treatment, or death due to any cause.	From randomisation until the start date of the second subsequent anti cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (anticipated to be up to 64 months).
Secondary	Progression Free Survival 2 (PFS2)	PFS2 will be defined as the time from the randomisation to the earliest progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice based on radiological or clinical progression.	From the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death (anticipated to be up to 64 months).
Secondary	Pharmacokinetics of Dato-DXd in combination with durvalumab	Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload) in plasma.	From first dose to end of treatment (anticipated to be up to 33 months).
Secondary	Immunogenicity of Dato-DXd in combination with durvalumab	Presence of antidrug antibodies for Dato-DXd (confirmatory results: positive or negative, titres).	From first dose to end of treatment safety follow-up (anticipated to be up to 33 months).
Secondary	Safety and tolerability of Dato-DXd + durvalumab as compared with ICC + pembrolizumab	Safety and tolerability will be evaluated in the safety population in terms of AEs.	From first dose to end of treatment safety follow-up (anticipated to be up to 33 months).