A Study of Durvalumab as Consolidation Therapy in Non-Small Cell Lung Cancer Patients

Carcinoma, Non-Small-Cell Lung Clinical Trial

— PACIFIC-5  

Official title:

A Phase III, Randomised,Double-Blind,Placebo-Controlled,Study of Durvalumab as Consolidation Therapy in Patients With Locally Advanced,Unresectable NSCLC, Who Have Not Progressed Following Definitive, Platinum-Based Chemoradiation Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03706690
• Other study ID #: D933YC00001
• Secondary ID: 2018-002294-22
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 27, 2018
• Est. completion date: March 16, 2027

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, randomised, double-blind, placebo-controlled, multicentre study assessing the efficacy and safety of durvalumab compared with placebo, as consolidation therapy in patients with locally advanced, unresectable, non-small cell lung cancer (Stage III), who have not progressed following definitive, platinum-based, chemoradiation therapy.

Description:

Approximately 400 patients will be randomized in a 2:1 to receive treatment with durvalumab or placebo therapy. The primary objective of this study is to assess the efficacy of durvalumab treatment compared with placebo in terms of PFS.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 407
• Est. completion date: March 16, 2027
• Est. primary completion date: June 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Age=18 years

2. Documented NSCLC and present with locally advanced, unresectable (Stage III) disease;

3. Receipt of concurrent or sequential chemoradiation therapy,

4. No progression following definitive, platinum-based, concurrent or sequential chemoradiation therapy

5. World Health Organization (WHO) PS of 0 or 1;

6. No prior exposure to any anti CTLA-4, anti-PD-1, anti-PD-L1, or anti PD L2 antibodies, excluding therapeutic anticancer vaccines

7. Adequate organ and marrow function required

8. Life expectancy of at least 12 weeks

9. Tumor PD-L1 status, with the Ventana SP263 PD-L1 IHC assay determined by a reference laboratory, must be known prior to randomization.

10. Tumour sample requirements are as follows: Provision of a tumour tissue sample (newly acquired sample <=3 months old is preferred, but an archived sample <=6 months old is acceptable) in a quantity sufficient to allow for analysis.

Exclusion Criteria:

1. History of allogeneic organ transplantation, or another primary malignancy, or active primary immunodeficiency.

2. Active or prior documented autoimmune or inflammatory disorders

3. Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent

4. Active infection including tuberculosis hepatitis B hepatitis C (HCV), or human immunodeficiency virus (positive human immunodeficiency virus [HIV] 1/2 antibodies).

5. Mixed small cell and NSCLC histology, sarcomatoid variant

6. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade =2 from the prior chemoradiation therapy.

7. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Durvalumab
Durvalumab 1500 mg every 4 weeks [q4w] intravenously [iv] until clinical progression/ deterioration or confirmed radiological progression.

Other:
• Placebo
Matching placebo for infusion every 4 weeks iv until clinical progression/deterioration or confirmed radiological progression

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
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	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Linhai
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Ningbo
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Ürümqi
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Yangzhou
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	HongKong
India	Research Site	Bangalore
India	Research Site	Bengaluru
India	Research Site	Karamsad
India	Research Site	Kolkata
India	Research Site	Nasik
India	Research Site	Vadodara
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Cdmx
Mexico	Research Site	Culiacán
Mexico	Research Site	México
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Mexico	Research Site	San Luis Potosí
Philippines	Research Site	Bacolod
Philippines	Research Site	Baguio City
Philippines	Research Site	Cagayan De Oro City
Philippines	Research Site	Cebu
Philippines	Research Site	Davao City
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Philippines	Research Site	San Juan
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Poznan
Poland	Research Site	Tomaszów Mazowiecki
Poland	Research Site	Warszawa
Russian Federation	Research Site	Kazan, Tatarstan
Russian Federation	Research Site	Kirov
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Murmansk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Samara
Russian Federation	Research Site	Saransk
Russian Federation	Research Site	Volgograd
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Konya
Turkey	Research Site	Malatya

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

China,  Hong Kong,  India,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Russian Federation,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) according to RECIST 1.1.	To assess the efficacy of durvalumab treatment compared with placebo in terms of PFS.	from date of randomisation until disease progression, assessed up to 29 months.
Secondary	The efficacy of durvalumab treatment compared to placebo in terms of Overall Survival (OS).	To further assess the efficacy of durvalumab compared with placebo in terms of OS.	from date of randomisation until the date of death, assessed up to 65 months.
Secondary	The efficacy of durvalumab treatment compared to placebo in terms of proportion of patients alive at 24 months (OS24) from randomisation.	To further assess the efficacy of durvalumab compared with placebo in terms of OS24.	at 24 months from participants' randomisation.
Secondary	Objective Response Rate (ORR) assessed by BICR according to RECIST 1.1.	To further assess the efficacy of durvalumab compared with placebo in terms of ORR.	from date of randomisation until progression, or the last evaluable assessment in the absence of progression, assessed up to 29 months.
Secondary	Duration of Response (DoR) assessed by BICR according to RECIST 1.1.	To further assess the efficacy of durvalumab compared with placebo in terms of DOR.	from date of randomisation until progression, or the last evaluable assessment in the absence of progression, assessed up to 29 months.
Secondary	Proportion of patients alive and progression free from randomisation to second progression (PFS2) as defined by local standard clinical practice.	The date of PFS2 assessment and Investigator opinion of progression status (progressed or non-progressed) at each assessment will be recorded in the PFS2 eCRF.	from randomisation to second progression. assessed up to 65 months.
Secondary	Proportion of patients alive and progression free at 12 months from randomisation (PFS12) assessed by BICR according to RECIST 1.1.	To further assess the efficacy of durvalumab compared with placebo in terms of PFS12.	at 12 months from participants' randomisation.
Secondary	Proportion of patients alive and progression free at 18 months from randomisation (PFS18) assessed by BICR according to RECIST 1.1.	To further assess the efficacy of durvalumab compared with placebo in terms of PFS18.	at 18 months from participants' randomisation.
Secondary	Proportion of patients at time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1.	To further assess the efficacy of durvalumab compared with placebo in terms of TTDM.	date of randomisation until the first date of distant metastasis or death in the absence of distant metastasis, assessed up to 65 months.
Secondary	Concentration of durvalumab in blood and non-compartmental PK parameters (such as peak concentration and trough, as data allow) (sparse sampling)	To assess the PK of durvalumab	at scheduled visits from randomisation to 3months after treatment discontinuation.
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	All AE data will be listed and the treatment-emergence status will be flagged in the listing.	from randomisation until 3 months after treatment discontinuation.
Secondary	Detection of ADA neutralising antibodies titres for all randomised patients	To investigate the immunogenicity of durvalumab	at scheduled visits from randomisation to 6months after treatment discontinuation.
Secondary	IHC analysis of tumoural PD-L1 expression and spatial distribution within the tumour microenvironment relative to efficacy outcome OS.	To investigate the relationship between a patient's baseline tumour PD-L1 expression and OS with durvalumab compared with placebo.	from date of randomisation until the date of death from any cause, whichever came first, assessed up to 65 months.
Secondary	IHC analysis of tumoural PD-L1 expression and spatial distribution within the tumour microenvironment relative to efficacy outcome PFS.	To investigate the relationship between a patient's baseline tumour PD-L1 expression and PFS with durvalumab compared with placebo.	from date of randomisation until disease progression, assessed up to 29 months.
Secondary	IHC analysis of tumoural PD-L1 expression and spatial distribution within the tumour microenvironment relative to efficacy outcome ORR.	To investigate the relationship between a patient's baseline tumour PD-L1 expression and ORR with durvalumab compared with placebo.	from date of randomisation until progression, or the last evaluable assessment in the absence of progression, assessed up to 29 months.