Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations

NSCLC Clinical Trial

— AVANZAR  

Official title:

A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05687266
• Other study ID #: D926NC00001
• Secondary ID: 2021-004606-21
• Status: Recruiting
• Phase: Phase 3
• Start date: December 29, 2022
• Est. completion date: February 22, 2027

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, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).

Description:

Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment.

The primary objectives of the study are to demonstrate superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of Progression Free Survival (PFS) by BICR and Overall Survival (OS) in first-line treatment of TROP2 biomarker positive participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1280
• Est. completion date: February 22, 2027
• Est. primary completion date: February 22, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion:

• Participants = 18 years at screening

• Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease

• Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).

Testing is not required for tumors with squamous histology, with exceptions.

• ECOG PS of 0 or 1

• Archival tumour tissue

• Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion:

• Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC

• History of another primary malignancy with exceptions

• Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade = 1 or baseline, with exceptions.

• Spinal cord compression or clinically or radiologically active brain metastases

• History of leptomeningeal carcinomatosis.

• Known active or uncontrolled hepatitis B or C virus infection.

• Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.

• Clinically significant corneal disease

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• Datopotamab deruxtecan
Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
• Durvalumab
Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
• Carboplatin
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
• Pembrolizumab
Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle for a maximum of 35 cycles or 2 years (whichever occurs first).
• Cisplatin
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
• Pemetrexed
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
• Paclitaxel
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Rankweil
Austria	Research Site	Wien
Austria	Research Site	Wien
Brazil	Research Site	Blumenau
Brazil	Research Site	Florianópolis
Brazil	Research Site	Fortaleza
Brazil	Research Site	Londrina
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Taubaté
Brazil	Research Site	Vitoria
Bulgaria	Research Site	Panagyurishte
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Saint John	New Brunswick
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	St-Jerome	Quebec
Canada	Research Site	Sudbury	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Kunming
China	Research Site	Kunming
China	Research Site	Lanzhou
China	Research Site	Liuzhou
China	Research Site	Shandong
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shantou
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Shijiazhuang
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xiamen
China	Research Site	Yangzhou
China	Research Site	Zhengzhou
Denmark	Research Site	Herning
Denmark	Research Site	Næstved
Denmark	Research Site	Sønderborg
France	Research Site	Brest
France	Research Site	Clermont-Ferrand
France	Research Site	Creteil
France	Research Site	Gleize
France	Research Site	Montpellier
France	Research Site	Nimes
France	Research Site	Paris
France	Research Site	Paris CEDEX 14
France	Research Site	Rouen
France	Research Site	Saint-Quentin cedex
France	Research Site	Strasbourg Cedex
France	Research Site	Toulon Cedex 9
France	Research Site	Toulouse
France	Research Site	Tours
Germany	Research Site	Bad Berka
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt A. Main
Germany	Research Site	Gauting
Germany	Research Site	Gütersloh
Germany	Research Site	Hamburg
Germany	Research Site	Kassel
Germany	Research Site	Kiel
Germany	Research Site	Koblenz
Germany	Research Site	Minden
Germany	Research Site	Mönchengladbach
Germany	Research Site	Paderborn
Germany	Research Site	Rosenheim
Germany	Research Site	Velbert
Germany	Research Site	Würzburg
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Peiraias
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyöngyös - Mátraháza
Hungary	Research Site	Kaposvár
Hungary	Research Site	Pécs
Hungary	Research Site	Szekszárd
Hungary	Research Site	Szolnok
Hungary	Research Site	Törökbálint
India	Research Site	Calicut
India	Research Site	Delhi
India	Research Site	Delhi
India	Research Site	Jaipur
India	Research Site	Kolkata
India	Research Site	Madurai
India	Research Site	New Delhi
India	Research Site	Puducherry
Italy	Research Site	Firenze
Italy	Research Site	Lecco
Italy	Research Site	Messina
Italy	Research Site	Napoli
Italy	Research Site	Orbassano
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Peschiera Del Garda
Italy	Research Site	Rozzano
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Morioka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Natori-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Jinju-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	Suwon
Korea, Republic of	Research Site	Suwon-si
Mexico	Research Site	Cdmx
Mexico	Research Site	Del. Cuauhtemoc
Mexico	Research Site	Merida
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Mexico	Research Site	San Luis Potosí
Peru	Research Site	Arequipa
Peru	Research Site	Concepción
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Bydgoszcz
Poland	Research Site	Bystra
Poland	Research Site	Grudziadz
Poland	Research Site	Kielce
Poland	Research Site	Koszalin
Poland	Research Site	Olsztyn
Poland	Research Site	Pila
Poland	Research Site	Poznan
Poland	Research Site	Przemysl
Poland	Research Site	Racibórz
Poland	Research Site	Radom
Poland	Research Site	Siedlce
Poland	Research Site	Tomaszów Mazowiecki
Poland	Research Site	Wroclaw
Spain	Research Site	Girona
Spain	Research Site	Las Palmas de Gran Canaria
Spain	Research Site	Lugo
Spain	Research Site	Madrid
Spain	Research Site	Santander
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Sweden	Research Site	Gävle
Sweden	Research Site	Linköping
Sweden	Research Site	Lund
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan City
Taiwan	Research Site	Yung Kang City
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Cheltenham
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Middlesborough
United Kingdom	Research Site	Newcastle-Upon-Tyne
United Kingdom	Research Site	Taunton
United Kingdom	Research Site	Torquay
United States	Research Site	Appleton	Wisconsin
United States	Research Site	Asheville	North Carolina
United States	Research Site	Auburn	Washington
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Bettendorf	Iowa
United States	Research Site	Boulder	Colorado
United States	Research Site	Canton	Ohio
United States	Research Site	Clifton Park	New York
United States	Research Site	Columbus	Ohio
United States	Research Site	Covington	Louisiana
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Denton	Texas
United States	Research Site	Des Moines	Iowa
United States	Research Site	Duluth	Minnesota
United States	Research Site	East Hills	New York
United States	Research Site	East Syracuse	New York
United States	Research Site	Evergreen Park	Illinois
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fargo	North Dakota
United States	Research Site	Fort Belvoir	Virginia
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fountain Valley	California
United States	Research Site	Hannibal	Missouri
United States	Research Site	Henrico	Virginia
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	Iowa City	Iowa
United States	Research Site	Irving	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Crosse	Wisconsin
United States	Research Site	Lakeland	Florida
United States	Research Site	Lakewood	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Memphis	Tennessee
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Muncie	Indiana
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norfolk	Virginia
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Quincy	Illinois
United States	Research Site	Renton	Washington
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Salem	Oregon
United States	Research Site	San Antonio	Texas
United States	Research Site	Spokane	Washington
United States	Research Site	Springdale	Arkansas
United States	Research Site	Sugar Land	Texas
United States	Research Site	Tacoma	Washington
United States	Research Site	Toledo	Ohio
United States	Research Site	Tucson	Arizona
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Watertown	South Dakota
United States	Research Site	West Islip	New York
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	York	Pennsylvania
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Austria,  Brazil,  Bulgaria,  Canada,  China,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety of Dato-DXd in combination with durvalumab and carboplatin	Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE Version 5.0).	Approximately 4 years
Primary	Progression-Free Survival (PFS) in the TROP2 biomarker positive population	PFS is defined as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), or death due to any cause.	Approximately 3 Years
Primary	Overall Survival (OS) in the TROP2 biomarker positive population	OS is defined as the time from randomisation until the date of death due to any cause.	Approximately 4 years
Secondary	PFS in the Intent-to-Treat (ITT) population	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.	Approximately 3 years
Secondary	OS in the ITT population	OS is defined as the time from randomisation until the date of death due to any cause.	Approximately 4 years
Secondary	PFS in the TROP2 biomarker negative population	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.	Approximately 3 years
Secondary	OS in the TROP2 biomarker negative population	OS is defined as the time from randomisation until the date of death due to any cause.	Approximately 4 years
Secondary	Objective Response Rate (ORR) in the TROP2 biomarker positive and ITT populations	ORR is defined as the proportion of participants who have a confirmed Complete Response (CR) or confirmed Partial Response (PR), as determined by BICR and investigator per RECIST 1.1.	Approximately 4 years
Secondary	Duration of Response (DoR) in the TROP2 biomarker positive and ITT populations	DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR and investigator assessment or death due to any cause.	Approximately 4 years
Secondary	PFS in the TROP2 biomarker positive and ITT populations	PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator assessment, or death due to any cause.	Approximately 3 years
Secondary	Pharmacokinetics of Dato-DXd when combined with durvalumab and carboplatin.	Concentration of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a in plasma and pharmacokinetic (PK) parameters (such as peak and trough concentrations, as data allow; sparse sampling).	Approximately 4 years
Secondary	Anti-Drug Antibody (ADA) for Dato-DXd	The immunogenicity of Dato-DXd when combined with durvalumab and carboplatin.	Approximately 4 years
Secondary	Time to Second Progression or Death (PFS2) in the TROP2 biomarker positive and ITT populations	PFS2 is defined as the time from randomisation to the earliest of the progression events (following the initial progression), subsequent to first subsequent therapy, or death.	Approximately 4 years
Secondary	Clinical Outcome Assessments such as TTD in pulmonary symptoms (dyspnoea, cough and chest pain) as measured by the NSCLC-SAQ, and TTD in physical functioning as measured by PROMIS Physical Function short form 8c	TTD is defined as the time from randomisation until the date of deterioration.	Approximately 4 years