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
  • Sao Paulo, Brazil, 01246-000
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Ostrava, Czechia, 703 00
    • Research Site
  • Praha 2, 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
  • Gurgaon, India, 122001
    • Research Site
  • Karamsad, India, 388325
    • Research Site
  • Mumbai, India, 400053
    • Research Site
  • Nasik, India, 422005
    • Research Site
  • New Delhi, India, 110063
    • Research Site
  • Vadodara, India, 390007
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8603
    • Research Site
  • Fukuoka-shi, Japan, 812-8582
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site
  • Kyoto, Japan, 606-8507
    • Research Site
  • Nagoya-shi, Japan, 464-8681
    • Research Site
  • Osakasayama, Japan, 589-8511
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Research Site
  • Chungcheongbuk-do, Korea, Republic of, 28644
    • Research Site
  • Gyeongsangnam-do, Korea, Republic of, 52727
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 6351
    • 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
  • Iloilo, Philippines, 5000
    • Research Site
  • Iloilo City, Philippines, 5000
    • Research Site
  • Makati, Philippines, 1229
    • Research Site
  • Manila, Philippines, 1015
    • Research Site
  • Quezon City, Philippines
    • Research Site
  • Taguig City, Philippines, 1634
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Elbląg, Poland, 02-300
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Research Site
  • Chelyabinsk, Russian Federation, 454087
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 115533
    • Research Site
  • Moscow, Russian Federation, 125367
    • Research Site
  • Omsk, Russian Federation, 644013
    • Research Site
  • Rostov-on-Don, Russian Federation, 344037
    • Research Site
  • Saint-Petersburg, Russian Federation, 197758
    • 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
  • Ankara, Turkey
    • Research Site
  • Ankara, Turkey, 06230
    • Research Site
  • Antalya, Turkey, 07059
    • Research Site
  • Diyarbakir, Turkey, 21280
    • Research Site
  • Istanbul, Turkey, 34030
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • 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	Time Frame
Progression-free survival (PFS)	From date of randomization until the date of objective disease progression or death, assessed up to 4 years.

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	From the date of randomization until death due to any cause, assessed up to 4 years.
Objective Response Rate (ORR)	From the date of Randomisaton until the date of objective disease progression or death, assessed up to 4 years
Overall Survival at 24 months	From the date of randomization until 24 months
Rate of complete response	From the date of Randomisaton until the date of objective disease progression or death, assessed up to 4 years
Duration of response (DoR)	From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression, assessed up to 4 years.
Disease Control Rate (DCR)	From the date of randomization until 24 weeks.
Time from randomization to second progression PFS2	From the date of randomization to the earliest progression event subsequent to that used for the PFS endpoint or death, up to 4 years
Time to death or distant metastasis (TTDM)	From the date of randomization to until the first date of distant metastasis or death in the absence of distant metastasis, assessed up to 4 years
Presence of ADA for durvalumab in combination with CRT	From the date of randomization until 6 months after date of last IP dose.
To assess symptoms and health-related QoL in patients treated with durvalumab + SoC CRT compared with placebo + SoC CRT using EORTC QLQ-C30 v3	From the date of randomisation until PFS2.
To assess symptoms and health-related QoL in patients treated with durvalumab + SoC CRT compared with placebo + SoC CRT using QLQ-LC13	From the date of randomisation until PFS2.
To assess the PK of durvalumab in blood (peak trough concentration) when in combination with CRT	From the date of randomization until 3 months after date of last IP dose.

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

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): September 7, 2023
• Study Completion (Estimated): October 31, 2024

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 (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Locally Advanced, Unresectable NSCLC, Carcinoma, NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Etoposide; Paclitaxel; Cisplatin; Durvalumab; Pemetrexed
• 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