A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

— PACIFIC-9  

Official title:

A Phase III, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05221840
• Other study ID #: D9078C00001
• Secondary ID: 2023-503999-24-0
• Status: Recruiting
• Phase: Phase 3
• Start date: February 7, 2022
• Est. completion date: May 31, 2030

Study information

• Verified date: April 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, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 999
• Est. completion date: May 31, 2030
• Est. primary completion date: May 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

• Participant must be = 18 years at the time of screening.
• Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
• Provision of a tumour tissue sample obtained prior to CRT
• Documented tumour PD-L1 status by central lab
• Documented EGFR and ALK wild-type status (local or central).
• Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
• Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
• Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
• WHO performance status of 0 or 1 at randomization
• Adequate organ and marrow function

EXCLUSION CRITERIA:

• 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 and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
• Mixed small cell and non-small cell lung cancer histology.
• Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
• Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
• Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
• Participants with =grade 2 pneumonitis from prior chemoradiation therapy.
• History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (= Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis - diagnosed in the past 6 months prior to randomization.
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
Durvalumab IV (intravenous infusion)
• Oleclumab
Oleclumab IV (intravenous infusion)
• Monalizumab
Monalizumab IV (intravenous infusion)

Other:
• Placebo
Placebo IV (intravenous infusion)

Locations

Country	Name	City	State
Australia	Research Site	Box Hill
Australia	Research Site	East Melbourne
Australia	Research Site	Elizabeth Vale
Australia	Research Site	Gosford
Australia	Research Site	Heidelberg
Australia	Research Site	Kogarah
Australia	Research Site	South Brisbane
Australia	Research Site	St Albans
Australia	Research Site	St. Leonards
Australia	Research Site	Westmead
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Florianópolis
Brazil	Research Site	Fortaleza
Brazil	Research Site	Jaú
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Uberlândia
Brazil	Research Site	Vitoria
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	Toronto	Ontario
China	Research Site	Anyang
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Jieyang
China	Research Site	Kunming
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Nanning
China	Research Site	Nantong
China	Research Site	Neijiang
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Shaoguan
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Zhanjiang
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou City
China	Research Site	Zhongshan
China	Research Site	Zhuhai
Colombia	Research Site	Barranquilla
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogotá
Colombia	Research Site	Bogota D.C.
Colombia	Research Site	Medellin
Colombia	Research Site	Valledupar
France	Research Site	Avignon Cedex 9
France	Research Site	Besançon Cedex
France	Research Site	Bordeaux
France	Research Site	Clermont-Ferrand
France	Research Site	Creteil Cedex
France	Research Site	Lorient cedex
France	Research Site	Marseille Cedex 20
France	Research Site	Montpellier
France	Research Site	Paris Cedex 5
France	Research Site	Rennes Cedex 9
France	Research Site	Rouen
France	Research Site	Toulouse CEDEX 09
France	Research Site	Villejuif Cedex
Germany	Research Site	Erfurt
Germany	Research Site	Erlangen
Germany	Research Site	Essen
Germany	Research Site	Esslingen
Germany	Research Site	Georgsmarienhuette
Germany	Research Site	Guetersloh
Germany	Research Site	Hannover
Germany	Research Site	Oldenburg
Germany	Research Site	Würzburg
Italy	Research Site	Brescia
Italy	Research Site	Firenze
Italy	Research Site	Lucca
Italy	Research Site	Meldola
Italy	Research Site	Orbassano
Italy	Research Site	Parma
Italy	Research Site	Pavia
Italy	Research Site	Roma
Japan	Research Site	Himeji-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kurume-shi
Japan	Research Site	Natori-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Tokushima-shi
Japan	Research Site	Toon-shi
Japan	Research Site	Wakayama-shi
Korea, Republic of	Research Site	Changwon-si
Korea, Republic of	Research Site	Cheongju-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	Suwon
Korea, Republic of	Research Site	Suwon-si
Peru	Research Site	Arequipa
Peru	Research Site	Concepción
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Trujillo
Poland	Research Site	Brzozów
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Koszalin
Poland	Research Site	Poznan
Poland	Research Site	Siedlce
Poland	Research Site	Tomaszów Mazowiecki
Poland	Research Site	Warszawa
Portugal	Research Site	Alcabideche
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Loures
Portugal	Research Site	Porto
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Yekaterinburg
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Granada
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Valencia
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei 112
Taiwan	Research Site	Taoyuan City
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Lampang
Thailand	Research Site	Muang
Thailand	Research Site	Muang
Thailand	Research Site	Mueang
Thailand	Research Site	Naimuang
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Diyarbakir
Turkey	Research Site	Goztepe Istanbul
Turkey	Research Site	Karsiyaka
Ukraine	Research Site	Chernihiv
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kropyvnytskyi
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site	Zaporizhzhia
United Kingdom	Research Site	Belfast
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Hampshire
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Middlesborough
United Kingdom	Research Site	Poole
United Kingdom	Research Site	Rhyl
United Kingdom	Research Site	Torquay
United Kingdom	Research Site	Truro
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Annapolis	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Billings	Montana
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Duluth	Minnesota
United States	Research Site	Duluth	Minnesota
United States	Research Site	Fairfax	Virginia
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Lexington	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Middletown	New York
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New Albany	Indiana
United States	Research Site	New Haven	Connecticut
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Richland	Washington
United States	Research Site	Richmond	Virginia
United States	Research Site	Ridgewood	New Jersey
United States	Research Site	San Diego	California
United States	Research Site	Scarborough	Maine
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Spokane	Washington
United States	Research Site	Stuart	Florida
United States	Research Site	Tacoma	Washington
United States	Research Site	Urbana	Illinois
United States	Research Site	Waterloo	Iowa
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,  Australia,  Brazil,  Canada,  China,  Colombia,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Peru,  Poland,  Portugal,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Surival (PFS)	Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.	Up to 5 years after first patient randomized.
Secondary	Overall Survival (OS)	Overall survival (OS)	Up to 9 years after first patient randomized
Secondary	Objective response rate (ORR)	Objective response rate (ORR) per RECIST 1.1 as assessed by BICR	Up to 5 years after first patient randomized
Secondary	Overall survival (OS) at 24 months	Overall survival (OS) at 24 months	Up to 9 years after first patient randomized
Secondary	Duration of response (DoR)	Duration of response (DoR) per RECIST 1.1 as assessed by BICR	Up to 5 years after first patient randomized
Secondary	Progression free survival (PFS) at 6, 12, 18, and 24 months	Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR	From date of randomization until 24 months
Secondary	Time from randomization to second progression (PFS2)	Time from randomization to second progression (PFS2)	Up to 5 years after first patient randomized
Secondary	Time from randomization to first date of distant metastasis or death (TTDM)	Time from randomization to first date of distant metastasis or death (TTDM)	Up to 5 years after first patient randomized
Secondary	Time from randomization to start date of first subsequent therapy (TFST)	Time from randomization to start date of first subsequent therapy (TFST)	Up to 9 years after first patient randomized
Secondary	Progression free survival (PFS) as assessed by Investigator	Progression free survival (PFS) as assessed by Investigator	Up to 5 years after first patient randomized
Secondary	IHC analysis of PD-L1 TC expression	IHC analysis of PD-L1 TC expression relative to efficacy outcomes	Up to 5 years after first patient randomized
Secondary	Concentration of Durvalumab	To assess the Pharmacokinetics of Durvalumab when in combination with Monalizumab or Oleclumab - serum peak and trough concentrations	From date of randomization until 3 months after date of last IP dose
Secondary	Anti-drug antibodies (ADAs)	The immunogenicity of durvalumab, oleclumab, and monalizumab as assessed by presence of anti-drug antibodies (ADAs)	From date of randomization until 3 months after date of last IP dose
Secondary	Time to deterioration in pulmonary symptoms (TTFCD)	Time to deterioration in pulmonary symptoms (TTFCD)	Up to 5 years after last patient randomized
Secondary	Concentration of Oleclumab	To assess the Pharmacokinetics of Oleclumab when in combination with Durvulumab - serum peak and trough concentrations	From date of randomization until 3 months after last dose of IP
Secondary	Concentration of Monalizumab	To assess the Pharmacokinetics of Monalizumab when in combination with Durvalumab - serum peak and trough concentrations	From date of randomization until 3 months after last dose of IP

External Links

•   Lung Cancer Study Locator details