A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based Chemotherapy

Advanced or Metastatic Non-Small Cell Lung Cancer Clinical Trial

— LATIFY  

Official title:

A Phase III, Open-label, Randomised, Multicentre Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations, and Whose Disease Has Progressed On or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy: LATIFY

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05450692
• Other study ID #: D533BC00001
• Secondary ID: 2022-000493-26
• Status: Recruiting
• Phase: Phase 3
• Start date: September 15, 2022
• Est. completion date: May 22, 2025

Study information

• Verified date: March 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 study will assess the efficacy and safety of the combination of ceralasertib and durvalumab versus standard of care docetaxel in patients with locally advanced and metastatic NSCLC after progression on prior anti-PD-(L)1 therapy and platinum-based chemotherapy.

Description:

This study will consist of two treatment arms (Groups A and B). Participants will be randomised in a 1:1 ratio to one of the two treatment groups: - Group A: Ceralasertib plus durvalumab combination therapy Each 28-day cycle will begin with ceralasertib administered orally followed by durvalumab administered intravenously. - Group B: Docetaxel monotherapy Each 21-day cycle will begin with the administration of docetaxel.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 580
• Est. completion date: May 22, 2025
• Est. primary completion date: May 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented NSCLC that is locally advanced or metastatic according to Version 8 of the IASLC Staging Manual in Thoracic Oncology.
• Documented epidermal growth receptor factor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type status as determined at a local laboratory.
• Documented radiological PD whilst on or after receiving the most recent treatment regimen.
• Eligible for second- or third-line therapy and must have received an anti-PD-(L)1 therapy and a platinum doublet containing therapy for locally advanced or metastatic NSCLC either separately or in combination.
• Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0 or 1.
• Adequate organ function and marrow reserve
• Minimum life expectancy of 12 weeks.
• Body weight > 30 kg and no cancer-associated cachexia.
• Negative pregnancy test (serum test) for women of childbearing potential (WOCBP).

Exclusion Criteria:

• Participant with mixed SCLC and NSCLC histology.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 5 years before the first dose of study intervention.
• Persistent toxicities (CTCAE Grade > 2) caused by previous anticancer therapy.
• Active or prior documented autoimmune or inflammatory disorders.
• Participants who have received more than one line of prior anti-PD-(L)1, either alone or in any combination.
• Participants:

1. Must not have experienced a toxicity that led to permanent discontinuation of the prior anti-PD(L)1 therapy.

2. All AEs while receiving prior anti-PD(L)1 therapy must have completely resolved.

3. Must not have experienced a Grade = 3 immune-mediated adverse event (imAE) or an immune-related neurologic or ocular AE of any grade while receiving prior anti-PD(L)1 therapy.

4. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.

• Participants who have received more than one prior line of platinum-based chemotherapy in metastatic setting.
• Participants who have received a prior ataxia telangiectasia and Rad3-related protein (ATR) inhibitor.

Related Conditions & MeSH terms

• Advanced or Metastatic Non-Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Ceralasertib
Participants will receive ceralasertib oral tablets.
• Durvalumab
Participants will receive durvalumab as an intravenous infusion.
• Docetaxel
Participants will received docetaxel as an intravenous infusion.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Cordoba
Argentina	Research Site	Pergamino
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	San Juan
Argentina	Research Site	Viedma
Australia	Research Site	Elizabeth Vale
Australia	Research Site	Lismore
Australia	Research Site	Murdoch
Australia	Research Site	Wendouree
Belgium	Research Site	Charleroi
Belgium	Research Site	Libramont-Chevigny
Belgium	Research Site	Roeselare
Brazil	Research Site	Fortaleza
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Baoding
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Deyang
China	Research Site	Ganzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Linyi
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Qingdao
China	Research Site	Taiyuan
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xingtai
China	Research Site	Yantai
China	Research Site	Zhanjiang
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
France	Research Site	Angers
France	Research Site	Clamart Cedex
France	Research Site	Clermont Ferrand
France	Research Site	Creteil
France	Research Site	Lyon
France	Research Site	Montpellier
France	Research Site	Nantes cedex 1
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Pessac
France	Research Site	Saint Herblain Cedex
France	Research Site	Saint-Quentin cedex
France	Research Site	Vantoux
France	Research Site	Villefranche Sur Saone
France	Research Site	Villejuif Cedex
Germany	Research Site	Berlin
Germany	Research Site	Freiburg
Germany	Research Site	Gauting
Germany	Research Site	Karlsruhe
Germany	Research Site	Kempten
Germany	Research Site	Löwenstein
Germany	Research Site	Moers
Germany	Research Site	Münster
Germany	Research Site	Ulm
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	King's Park
Hong Kong	Research Site	Tun Mun
Hungary	Research Site	Budapest
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Törökbálint
Hungary	Research Site	Zalaegerszeg
India	Research Site	Bhubaneswar
India	Research Site	Jaipur
India	Research Site	Jaipur
India	Research Site	Mumbai
India	Research Site	Pune
India	Research Site	Surat
Ireland	Research Site	Cork
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin 4
Ireland	Research Site	Limerick
Italy	Research Site	Aviano
Italy	Research Site	Catania
Italy	Research Site	Livorno
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Verona
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kurashiki-shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Toyoake-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Cheongju-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	Suwon
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Tilburg
Netherlands	Research Site	Zutphens
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Kraków
Poland	Research Site	Poznan
Poland	Research Site	Skórzewo
Poland	Research Site	Torun
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Constanta
Romania	Research Site	Craiova
Romania	Research Site	Craiova
Romania	Research Site	Floresti
Romania	Research Site	Oradea
Romania	Research Site	Timisoara
Romania	Research Site	Timisoara
Serbia	Research Site	Belgrad
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Kragujevac
Spain	Research Site	A Coruña
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Castello de la Plana
Spain	Research Site	Cordoba
Spain	Research Site	Hospitalet deLlobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Malaga
Spain	Research Site	Orense
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Pamplona
Spain	Research Site	Pozuelo de Alarcon
Spain	Research Site	Sabadell
Spain	Research Site	Servilla
Spain	Research Site	Zaragoza
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan City
Taiwan	Research Site	Yunlin
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Stevenage
United Kingdom	Research Site	Sutton
United Kingdom	Research Site	Wirral
United States	Research Site	Allentown	Pennsylvania
United States	Research Site	Appleton	Wisconsin
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bethesda	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Birmingham	Alabama
United States	Research Site	Canton	Ohio
United States	Research Site	Cerritos	California
United States	Research Site	Chandler	Arizona
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cleveland	Ohio
United States	Research Site	Corona	California
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Greeley	Colorado
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hattiesburg	Mississippi
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jamaica	New York
United States	Research Site	Kingwood	Texas
United States	Research Site	Lacey	Washington
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lexington	Kentucky
United States	Research Site	Los Alamitos	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Marietta	Georgia
United States	Research Site	Miami	Florida
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orlando	Florida
United States	Research Site	Peoria	Illinois
United States	Research Site	Phoenix	Arizona
United States	Research Site	Providence	Rhode Island
United States	Research Site	Rockville	Maryland
United States	Research Site	Spokane	Washington
United States	Research Site	Tucson	Arizona
United States	Research Site	Whittier	California
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Hong Kong,  Hungary,  India,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Serbia,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	The superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel will be demonstrated by assessment of OS (HR with 95% CI and p-value) in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. OS is defined as time from randomisation until the date of death due to any cause.	Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years)
Secondary	Progression-Free Survival (PFS)	PFS will be defined as the time from the date of randomisation until the date of objective PD.	Up to 3 years
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participant who have a Complete Response (CR) or Partial Response (PR) per RECIST 1.1.	Up to 3 years
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.	Up to 3 years
Secondary	Time To Response (TTR)	TTR is defined as the time from randomisation until the date of first documented objective response.	Up to 3 years
Secondary	Disease Control Rate (DCR)	DCR at 18 weeks is defined as the percentage of participants who have a CR or PR or who have stable disease (SD) for at least 17 weeks.	At Week 18
Secondary	Time to second progression or death (PFS2)	Time from randomisation to PFS2 will be defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.	Up to 3 years
Secondary	Overall Survival (OS) at 12 months	OS is defined as time from randomisation until the data of death due to any cause.	At 12 months
Secondary	Time To Deterioration (TTD) of health-related quality of life (QoL)	TTD is defined as the time from randomisation until the date of first confirmed deterioration.	Up to 3 years
Secondary	TTD of physical function	TTD in physical functioning is measured by the EORTC QLQ-C30 Physical Function subscale of the EORTC QLQ-C30.	Up to 3 years
Secondary	Plasma concentrations for ceralasertib plus durvalumab combination therapy	The PK plasma concentration of ceralasertib when administered in combination with durvalumab will be assessed.	Up to 3 years
Secondary	Number of participants with Adverse Evens (AEs)	The safety and tolerability of ceralasertib plus durvalumab combination therapy as compared with docetaxel will be assessed.	Up to 3 years