A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC

Non-Small Cell Lung Cancer Clinical Trial

— PACIFIC-8  

Official title:

A Phase III, Randomised, Double-blind, Placebo-controlled, Multicentre, International Study of Durvalumab Plus Domvanalimab(AB154) in Participants With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer Whose Disease Has Not Progressed Following Definitive Platinum-based Concurrent Chemoradiation Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05211895
• Other study ID #: D9075C00001
• Secondary ID: 2021-004327-32
• Status: Recruiting
• Phase: Phase 3
• Start date: February 18, 2022
• Est. completion date: August 30, 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, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive platinum-based cCRT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 860
• Est. completion date: August 30, 2030
• Est. primary completion date: June 27, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

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

2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease

3. Provision of a tumour tissue sample obtained prior to CRT

4. Documented tumour PD-L1 status = 1% by central lab

5. Documented EGFR and ALK wild-type status (local or central).

6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy

7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy

8. 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.

9. WHO performance status of 0 or 1 at randomization

10. Adequate organ and marrow function

EXCLUSION CRITERIA:

1. 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. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease.

2. Mixed small cell and non-small cell lung cancer histology.

3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.

4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.

5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).

6. Participants with = grade 2 pneumonitis from prior chemoradiation therapy.

7. 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

8. Active or prior documented autoimmune or inflammatory disorders (with exceptions)

9. Active EBV infection, or known or suspected chronic active EBV infection at screening

10. 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)
• Domvanalimab
Domvanalimab IV (Intravenous infusion)

Other:
• Placebo
Placebo IV (Intravenous infusion)

Locations

Country	Name	City	State
Belgium	Research Site	Brussels
Belgium	Research Site	Edegem
Belgium	Research Site	Haine-Saint-Paul
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Belgium	Research Site	Sint-Niklaas
Brazil	Research Site	Londrina
Brazil	Research Site	Porto Velho
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Taubaté
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Montreal	Quebec
Chile	Research Site	Las Condes
Chile	Research Site	Puerto Montt
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
France	Research Site	Aix en Provence
France	Research Site	Angers
France	Research Site	Bobigny
France	Research Site	Clermont-Ferrand
France	Research Site	Lille
France	Research Site	Paris Cedex 14
France	Research Site	Pau cedex
France	Research Site	Quimper cedex
France	Research Site	Saint Gregoire
France	Research Site	Saint-Quentin cedex
France	Research Site	Vantoux
France	Research Site	Villeurbanne
Germany	Research Site	Berlin
Germany	Research Site	Berlin-Zehlendorf
Germany	Research Site	Braunschweig
Germany	Research Site	Chemnitz
Germany	Research Site	Georgsmarienhuette
Germany	Research Site	Giessen
Germany	Research Site	Halle
Germany	Research Site	Hamburg
Germany	Research Site	Homburg
Germany	Research Site	Koblenz
Germany	Research Site	Köln
Germany	Research Site	Krefeld
Germany	Research Site	Löwenstein
Germany	Research Site	Moers
Germany	Research Site	München
Germany	Research Site	Regensburg
Germany	Research Site	Regensburg
Germany	Research Site	Tübingen
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Holargos, Athens
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	Hong Kong
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Deszk
Hungary	Research Site	Gyor
Hungary	Research Site	Salgótarján
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Törökbálint
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Delhi
India	Research Site	Gurgaon
India	Research Site	Howrah
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	Kolkata
India	Research Site	Marg Jaipur
India	Research Site	Mohali
India	Research Site	Namakkal
India	Research Site	New Delhi
India	Research Site	New Delhi
Italy	Research Site	Bergamo
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Udine
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kashihara-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Tokyo
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Incheon
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
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Selangor
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Cdmx
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Monterrey
Mexico	Research Site	Oaxaca
Mexico	Research Site	Sonora
Mexico	Research Site	Veracruz
Norway	Research Site	Bodø
Norway	Research Site	Gjøvik
Norway	Research Site	Oslo
Norway	Research Site	Trondheim
Philippines	Research Site	Bacolod
Philippines	Research Site	Iloilo City
Philippines	Research Site	Muntinlupa City
Philippines	Research Site	Pasig City
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Gliwice
Poland	Research Site	Gliwice
Poland	Research Site	Katowice
Poland	Research Site	Lódz
Poland	Research Site	Wroclaw
Poland	Research Site	Zielona Góra
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Iasi
Romania	Research Site	Oradea
Romania	Research Site	Sibiu
Romania	Research Site	Suceava
Romania	Research Site	Timisoara
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Parktown
South Africa	Research Site	Pretoria
Spain	Research Site	Bilbao (Vizcaya)
Spain	Research Site	Castello de la Plana
Spain	Research Site	Cordoba
Spain	Research Site	El Palmar
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Sabadell (Barcelona)
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Lausanne
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	New-Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adapazari
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Çankaya
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Konya
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Cheltenham
United Kingdom	Research Site	High Heaton/Newcastle Upon Tyn
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United States	Research Site	Arlington	Virginia
United States	Research Site	Asheville	North Carolina
United States	Research Site	Asheville	North Carolina
United States	Research Site	Baltimore	Maryland
United States	Research Site	Buffalo	New York
United States	Research Site	Chandler	Arizona
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Columbus	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Elmhurst	Illinois
United States	Research Site	Florham Park	New Jersey
United States	Research Site	Fort Belvoir	Virginia
United States	Research Site	Fort Sam Houston	Texas
United States	Research Site	Fountain Valley	California
United States	Research Site	Jacksonville	Florida
United States	Research Site	Johnson City	New York
United States	Research Site	Louisville	Kentucky
United States	Research Site	Macon	Georgia
United States	Research Site	Maywood	Illinois
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Naperville	Illinois
United States	Research Site	Nashville	Tennessee
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Augustine	Florida
United States	Research Site	Santa Rosa	California
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Spokane Valley	Washington
United States	Research Site	Washington	District of Columbia
United States	Research Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Arcus Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Chile,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Norway,  Philippines,  Poland,  Romania,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC = 50%.	Up to 8 years after first patient randomised
Secondary	Progression Free Survival (PFS)	Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC = 1%	Up to 8 years after first patient randomised
Secondary	Overall Survival (OS)	Overall Survival (OS)	Approximately 8 years after first patient randomized
Secondary	Objective Response Rate (ORR)	Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR	Approximately 8 years after first patient randomized
Secondary	Duration of Response (DoR)	Duration of Response (DoR) using BICR assessment according to RECIST 1.1	Approximately 8 years after first patient randomized
Secondary	Time from randomization to second progression (PFS2)	Time from randomization to second progression (PFS2)	Approximately 8 years after first patient randomized
Secondary	Time from randomization to first date of distant metastasis or death (TTDM)	Time from randomization until the first date of distant metastasis or death in the absence of distant metastasis (TTDM).	Approximately 8 years after first patient randomized
Secondary	Time to first subsequent therapy (TFST)	Time to first subsequent therapy (TFST)	Approximately 8 years after first patient randomized
Secondary	Concentration of Durvalumab and Domvanalimab	The pharmacokinetics (PK) of Durvalumab and Domvanalimab as determined by concentration	Approximately 12 weeks after last IP dose
Secondary	PFS6, PFS12, PFS18, PFS24	PFS at 6, 12, 18 and 24 months (proportion per Kaplan-Meier)	Approximately 6, 12, 18 and 24 months after last patient randomized
Secondary	Anti-Drug Antibodies (ADAs)	The immunogenicity of Durvalumab and domvanalimab as assessed by presence of Anti-Drug Antibodies (ADAs)	Approximately 12 weeks after last IP dose.
Secondary	Time to deterioration in pulmonary symptoms (TTFCD)	Time to deterioration in pulmonary symptoms (TTFCD)	Approximately 8 years after first patient randomized

External Links

•   1-844-432-3892 Lung Cancer Study Locator details to CT.gov for the US sites only