Clinical trial NCT03706690: A Study of Durvalumab as Consolidation Therapy in Non-Small Cell Lung Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: NSCLC
Double-Blind
PD-L1
MEDI4736
Durvalumab
PFS
OS
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-10-16
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] Set)
timeFrame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
measure: Progression-Free Survival (PFS) (Intent-to-Treat [ITT] Set)
timeFrame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
measure: Percentage of Participants Alive at 24 Months (OS24)
timeFrame: Month 24
measure: Objective Response Rate (ORR)
timeFrame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
measure: Duration of Response (DoR)
timeFrame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
measure: Percentage of Participants Alive and Progression-Free at 12 and 18 Months (PFS12 and PFS18)
timeFrame: Months 12 and 18
measure: Time From Randomization to Second Progression (PFS2)
timeFrame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
measure: Time to Death or Distant Metastases (TTDM)
timeFrame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
measure: Serum Concentration of Durvalumab
timeFrame: End of infusion on Cycle 1 Day 1, pre-infusion on Cycles 2 and 4 Day 1 and Month 3 follow-up (each cycle=28 days)
measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
timeFrame: Pre-dose on Day 1 of Cycles 1, 2 and 4 (each cycle=28 days)
measure: Change From Baseline in Patient-Reported Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Week 132
timeFrame: Baseline (Day 1) and Week 132
measure: Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Status Based on Overall Survival, Progression-Free Survival and Objective Response Rate
timeFrame: Up to 9 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Ürümqi
country: China
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: HongKong
country: Hong Kong
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Bengaluru
country: India
facility: Research Site
city: Karamsad
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Nasik
country: India
facility: Research Site
city: Vadodara
country: India
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Cdmx
country: Mexico
facility: Research Site
city: Culiacán
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: San Luis Potosí
country: Mexico
facility: Research Site
city: Bacolod
country: Philippines
facility: Research Site
city: Baguio City
country: Philippines
facility: Research Site
city: Cagayan De Oro City
country: Philippines
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: San Juan
country: Philippines
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Tomaszów Mazowiecki
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Kazan, Tatarstan
country: Russian Federation
facility: Research Site
city: Kirov
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Murmansk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Samara
country: Russian Federation
facility: Research Site
city: Saransk
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Konya
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
Study officials:
affiliation: Guangdong General Hospital, Guangdong Lung Cancer Institute
name: Yilong Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: