Study of Durvalumab Given With Chemoradiation Therapy in Patients With Unresectable Non-small Cell Lung Cancer

A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently With Platinum-based Chemoradiation Therapy in Patients With Locally Advanced, Unresectable NSCLC (Stage III) (PACIFIC2)

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + standard of care [SoC] CRT) in patients with locally advanced, unresectable NSCLC (Stage III).

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Cisplatin/ Etoposide; Drug: Carboplatin/ Paclitaxel; Drug: Pemetrexed/ Cisplatin; Drug: Pemetrexed/ Carboplatin; Radiation: Radiation; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 328
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Curitiba, Brazil, 81520-060
    • Research Site
  • Florianópolis, Brazil, 88034-000
    • Research Site
  • Fortaleza, Brazil, 60336-045
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Ribeirão Preto, Brazil, 14021-636
    • Research Site
  • Ribeirão Preto, Brazil, 14048900
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Ostrava, Czechia, 703 00
    • Research Site
  • Prague, Czechia, 128 08
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Budapest, Hungary, 1121
    • Research Site
  • Gyula, Hungary, 5700
    • Research Site
  • Győr, Hungary, 9024
    • Research Site
  • Törökbálint, Hungary, 2045
    • Research Site
• India
  • Bangalore, India, 560068
    • Research Site
  • Chennai, India, 600035
    • Research Site
  • Gūrgaon, India, 122001
    • Research Site
  • Karamsad, India, 388325
    • Research Site
  • Mumbai, India, 400053
    • Research Site
  • Nashik, India, 422005
    • Research Site
  • New Delhi, India, 110063
    • Research Site
  • Vadodara, India, 390007
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8603
    • Research Site
  • Fukuoka, Japan, 812-8582
    • Research Site
  • Kyoto, Japan, 606-8507
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Research Site
  • Nagoya, Japan, 464-8681
    • Research Site
  • Sayama, Japan, 589-8511
    • Research Site
  • Sendai, Japan, 980-0873
    • Research Site
  • Yokohama, Japan, 241-8515
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Research Site
  • Guadalajara, Mexico, 44280
    • Research Site
  • Mexico City, Mexico, 0 3100
    • Research Site
  • Mérida, Mexico, 97134
    • Research Site
  • México, Mexico, 04700
    • Research Site
  • Orizaba, Mexico, 94300
    • Research Site
• Peru
  • La Libertad, Peru, 13013
    • Research Site
  • Lima, Peru, 15033
    • Research Site
  • Lima, Peru, L27
    • Research Site
  • Lima, Peru, LIMA 27
    • Research Site
  • Lima, Peru, LIMA 34
    • Research Site
  • Lima, Peru, LIMA 41
    • Research Site
• Philippines
  • Cebu City, Philippines, 6000
    • Research Site
  • City of Taguig, Philippines, 1634
    • Research Site
  • Iloilo City, Philippines, 5000
    • Research Site
  • Makati, Philippines, 1229
    • Research Site
  • Manila, Philippines, 1015
    • Research Site
  • Quezon City, Philippines
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Elblag, Poland, 02-300
    • Research Site
  • Gdansk, Poland, 80-952
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
  • Warsaw, Poland, 02-781
    • Research Site
• Russia
  • Arkhangelsk, Russia, 163045
    • Research Site
  • Chelyabinsk, Russia, 454087
    • Research Site
  • Moscow, Russia, 115478
    • Research Site
  • Moscow, Russia, 115533
    • Research Site
  • Moscow, Russia, 125367
    • Research Site
  • Omsk, Russia, 644013
    • Research Site
  • Rostov-on-Don, Russia, 344037
    • Research Site
  • Saint Petersburg, Russia, 197758
    • Research Site
• South Korea
  • Busan, South Korea, 48108
    • Research Site
  • Chungcheongbuk-do, South Korea, 28644
    • Research Site
  • Gyeongsangnam-do, South Korea, 52727
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 6351
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Mueang, Thailand, 50200
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Research Site
  • Ankara, Turkey (Türkiye)
    • Research Site
  • Antalya, Turkey (Türkiye), 07059
    • Research Site
  • Diyarbakır, Turkey (Türkiye), 21280
    • Research Site
  • Istanbul, Turkey (Türkiye), 34030
    • Research Site
  • Izmir, Turkey (Türkiye), 35100
    • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Principal inclusion criteria :

• Subjects with histologically- or cytologically-documented NSCLC
• Locally advanced, unresectable (Stage III) NSCLC
• World Health Organisation (WHO) performance status 0-1
• At least one measurable lesion, not previously irradiated
• Must have a life expectancy of at least 12 weeks at randomization

Principal exclusion criteria :

• Receipt of prior or current cancer treatment, including but not limited to, radiation therapy, investigational agents, chemotherapy, Durvalumab and mAbs.
• Prior exposure to immune-mediated therapy, including but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti PD L2 antibodies, excluding therapeutic anticancer vaccines.
• History of allogeneic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness
• History of another primary malignancy / leptomeningeal carcinomatosis / active primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
• Mixed small cell and NSCLC histology
• Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling
• Known allergy or hypersensitivity to any of the IPs or any of the IP excipients.
• Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Durvalumab + platinum-based chemotherapy and radiation; Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: cisplatin/etoposide; carboplatin/paclitaxel; pemetrexed/cisplatin; pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Drug: Cisplatin/ Etoposide; Cisplatin/ Etoposide, as per standard of care; Drug: Carboplatin/ Paclitaxel; Carboplatin /Paclitaxel, as per standard of care; Drug: Pemetrexed/ Cisplatin; Pemetrexed / Cisplatin, as per standard of care; Drug: Pemetrexed/ Carboplatin; Pemetrexed / Carboplatin , as per standard of care; Radiation: Radiation; 5 fractions/ week for ~6 weeks (±3 days) (Total 60 Gy)
Placebo Comparator: Arm 2: Placebo + platinum-based chemotherapy and radiation; Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: cisplatin/etoposide; carboplatin/paclitaxel; pemetrexed/cisplatin; pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.	Drug: Cisplatin/ Etoposide; Cisplatin/ Etoposide, as per standard of care; Drug: Carboplatin/ Paclitaxel; Carboplatin /Paclitaxel, as per standard of care; Drug: Pemetrexed/ Cisplatin; Pemetrexed / Cisplatin, as per standard of care; Drug: Pemetrexed/ Carboplatin; Pemetrexed / Carboplatin , as per standard of care; Radiation: Radiation; 5 fractions/ week for ~6 weeks (±3 days) (Total 60 Gy); Other: Placebo; Placebo IV (intravenous infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions. Median PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The ORR per RECIST 1.1 using BICR was defined as the percentage of participants with a confirmed response of complete response (CR) or partial response (PR) based on all participants in the FAS. The CR was defined as disappearance of all target lesions since baseline. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions.	Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).
Overall Survival (OS)	The OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy. Median OS was calculated using the Kaplan-Meier technique.	From screening until confirmed PD, assessed up to the DCO date (a maximum of approximately 1988 days).
Percentage of Participants Alive at 24 Months From Randomization (OS24)	The OS24 was defined as the Kaplan-Meier estimate of OS at 24 months. Median OS24 was calculated using the Kaplan-Meier technique.	Month 24
Complete Response Rate (CRR)	The CRR per RECIST 1.1 using BICR was defined as the percentage of participants with a confirmed response of CR. The CR was defined as disappearance of all target lesions since baseline.	Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).
Duration of Response (DoR)	The DoR per RECIST 1.1 using BICR was defined as the time from the date of first documented response (which was subsequently confirmed) until the first date of documented progression or death in the absence of PD. The CR was defined as disappearance of all target lesions since baseline. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions. The DoR was calculated using the Kaplan-Meier technique.	Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).
Disease Control Rate (DCR)	The DCR at 24 weeks per RECIST 1.1 using BICR was defined as the percentage of participants who had a best objective response of CR or PR in the first 25 weeks (to allow for late assessment within the assessment window) or who had stable disease for >= 23 weeks after randomization (to allow for an early assessment within the ± 1 week assessment window).	Week 24
Time to Death or Distant Metastasis (TTDM)	The TTDM per RECIST 1.1 using BICR was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that was outside the radiation field according to RECIST 1.1 or proven by biopsy.	Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).
Time From Randomization to Second Progression (PFS2)	The PFS2 was defined as the time from the date of randomization to the earliest of the progression event (subsequent to that used for the primary variable PFS per Investigator assessment) or death. The date of the second progression was recorded by the Investigator and defined according to local standard clinical practice and could have involved any of objective radiological, symptomatic progression, or death. Median PFS2 was calculated using the Kaplan-Meier technique.	Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).
Serum Concentration of Durvalumab	Blood samples were collected to determine the concentration of durvalumab.	End of infusion on Week 0, pre-infusion on Weeks 4 and 12, and Month 3 follow-up
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab	Blood samples were collected to determine the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence was defined as the number of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence was defined as either treatment-induced (post-baseline ADA positive only) or treatment-boosted ADA (baseline positive ADA titer that was boosted to >= 4-fold during the study period). Treatment-induced ADA was defined as ADA positive only post-baseline and not detected at baseline. Persistently positive was defined as having at least 2 post-baseline ADA positive assessments with at least 16 weeks between the first and last positive assessment, or ADA positive at the last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment without fulfilling the conditions for persistently positive.	Pre-dose on Day 1 of Cycles 1, 2 and 4
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Average Over 12 Months	Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a total score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status scale with higher scores on the global health status/quality of life (QoL) and functioning scales representing better health status/function, but higher scores on symptom scales/items representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as a change from baseline of >=10.	At screening, 2, 4, 6, 8, 12, 16, and 20 weeks after randomization, then every 8 weeks ±1 week up to 52 weeks, and then every 12 weeks ±1 week thereafter until PFS2. Assessed up to 12 months.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is the development of any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A SAE is an AE occurring during any study phase, that fulfils 1 or more of the following criteria: death, life-threatening, in-participant hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital abnormality or birth defect, and an important medical event that may jeopardize the participant or may require medical treatment to prevent 1 of the outcomes listed above. AEs leading to discontinuation of study treatment were those with action taken was 'Drug Permanently Discontinued' for any study treatment.	From time of signature of informed consent up to 90 days after last dose of study treatment or up to the date of initiation of the first subsequent therapy, whichever occurs first, approximately 1988 days.

Other Outcome Measures

Outcome Measure	Time Frame
Adverse events	From the date of randomization until disease progression, assessed up to 4 years.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Jeffrey Bradley, MD, AstraZeneca

Publications and helpful links

Helpful Links

• SAP
• CSP
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): September 7, 2023
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: May 4, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Locally Advanced, Unresectable NSCLC, Carcinoma, NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Physical Phenomena; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin; Radiation; durvalumab; CP protocol; PE regimen
• Other Study ID Numbers: D933KC00001; 2017-004397-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes