A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC-9)

A Phase III, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy

This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Other: Placebo; Drug: Oleclumab; Drug: Monalizumab

• Study Type: Interventional
• Enrollment (Actual): 1051
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • East Melbourne, Australia, 3002
    • Research Site
  • Elizabeth Vale, Australia, 5112
    • Research Site
  • Gosford, Australia, 2250
    • Research Site
  • Heidelberg, Australia, 3084
    • Research Site
  • Kogarah, Australia, 2217
    • Research Site
  • South Brisbane, Australia, 4101
    • Research Site
  • St Albans, Australia, 3021
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Belo Horizonte, Brazil, 30380-090
    • Research Site
  • Florianópolis, Brazil, 88034-000
    • Research Site
  • Fortaleza, Brazil, 60336-232
    • Research Site
  • Jaú, Brazil, 17210-120
    • Research Site
  • Natal, Brazil, 59075-740
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90610-001
    • Research Site
  • Recife, Brazil, 52010-075
    • Research Site
  • São Paulo, Brazil, 01323-903
    • Research Site
  • Uberlândia, Brazil, 38408-150
    • Research Site
  • Vitória, Brazil, 29043-260
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Research Site
    • Hamilton, Ontario, Canada, L8V 5C2
      • Research Site
    • Kingston, Ontario, Canada, K7L 2V7
      • Research Site
    • London, Ontario, Canada, N6A 5W9
      • Research Site
    • Mississauga, Ontario, Canada, L5M 2N1
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Rimouski, Quebec, Canada, G5L 5T1
      • Research Site
• China
  • Anyang, China, 455000
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Guangzhou, China, 510062
    • Research Site
  • Guangzhou, China, 510700
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hangzhou, China, 310002
    • Research Site
  • Hefei, China, 230031
    • Research Site
  • Hefei, China, 133500
    • Research Site
  • Kunming, China, 650118
    • Research Site
  • Linhai, China, 317000
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanning, China, 530021
    • Research Site
  • Nantong, China, 226361
    • Research Site
  • Neijiang, China, 641000
    • Research Site
  • Ningbo, China, 315100
    • Research Site
  • Shaoguan, China, 512027
    • Research Site
  • Tianjin, China, 300060
    • Research Site
  • Wuhan, China, 430079
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Wuhan, China, 430071
    • Research Site
  • Zhanjiang, China, 524001
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
  • Zhengzhou, China, 450000
    • Research Site
  • Zhongshan, China, 528403
    • Research Site
• Colombia
  • Barranquilla, Colombia, 080020
    • Research Site
  • Bogota D.C., Colombia, 110131
    • Research Site
  • Medellín, Colombia, 050034
    • Research Site
  • Valledupar, Colombia, 200001
    • Research Site
• France
  • Avignon, France, 84918
    • Research Site
  • Besançon, France, 25030
    • Research Site
  • Bordeaux, France, 33075
    • Research Site
  • Clermont-Ferrand, France, 63000
    • Research Site
  • Créteil, France, 94010
    • Research Site
  • Lorient, France, 56322
    • Research Site
  • Marseille, France, 13015
    • Research Site
  • Montpellier, France, 34298
    • Research Site
  • Rennes, France, 35033
    • Research Site
  • Rouen, France, 76031
    • Research Site
  • Toulouse, France, 31059
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Erfurt, Germany, 99089
    • Research Site
  • Erlangen, Germany, 91054
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Esslingen am Neckar, Germany, 73730
    • Research Site
  • Georgsmarienhütte, Germany, 49124
    • Research Site
  • Gütersloh, Germany, 33332
    • Research Site
  • Hanover, Germany, 30459
    • Research Site
  • Oldenburg, Germany, 26121
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Italy
  • Brescia, Italy, 25123
    • Research Site
  • Florence, Italy, 50134
    • Research Site
  • Lucca, Italy, 55100
    • Research Site
  • Meldola, Italy, 47014
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Parma, Italy, 43126
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Roma, Italy, 00128
    • Research Site
• Japan
  • Himeji-shi, Japan, 670-8520
    • Research Site
  • Hiroshima, Japan, 730-0011
    • Research Site
  • Kashiwa, Japan, 227-8577
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Natori-shi, Japan, 981-1293
    • Research Site
  • Niigata, Japan, 951-8566
    • Research Site
  • Osaka, Japan, 541-8567
    • Research Site
  • Sendai, Japan, 980-0873
    • Research Site
  • Tokushima, Japan, 770-8503
    • Research Site
  • Toon-shi, Japan, 791-0295
    • Research Site
  • Wakayama, Japan, 641-8510
    • Research Site
• Peru
  • Lima, Peru, LIMA 34
    • Research Site
  • Lima, Peru, Lima 32
    • Research Site
  • Lima, Peru, 15038
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdansk, Poland, 80-952
    • Research Site
  • Koszalin, Poland, 75-581
    • Research Site
  • Poznan, Poland, 60-569
    • Research Site
  • Siedlce, Poland, 08-110
    • Research Site
  • Tomaszów Mazowiecki, Poland, 97-200
    • Research Site
  • Warsaw, Poland, 02-781
    • Research Site
• Portugal
  • Lisbon, Portugal, 1998-018
    • Research Site
  • Lisbon, Portugal, 1769-001
    • Research Site
  • Lisbon, Portugal, 1099-023
    • Research Site
  • Lisbon, Portugal, 1400-038
    • Research Site
  • Loures, Portugal, 2674-514
    • Research Site
  • Porto, Portugal, 4200-319
    • Research Site
• South Korea
  • Changwon-si, South Korea, 51353
    • Research Site
  • Cheongju-si, South Korea, 28644
    • Research Site
  • Seongnam-si, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Suwon, South Korea, 16499
    • Research Site
  • Suwon, South Korea, 16247
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Barcelona, Spain, 8003
    • Research Site
  • Granada, Spain, 18016
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Santiago de Compostela, Spain, 15706
    • Research Site
  • Valencia, Spain, 46010
    • Research Site
• Taiwan
  • Hsinchu, Taiwan, 300
    • Research Site
  • New Taipei City, Taiwan, 23561
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 402
    • Research Site
  • Taipei, Taiwan
    • Research Site
  • Taipei, Taiwan, 11490
    • Research Site
  • Taoyuan City, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10300
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Khon Kaen, Thailand, 40000
    • Research Site
  • Lampang, Thailand, 52000
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Muang, Thailand, 22000
    • Research Site
  • Mueang, Thailand, 20000
    • Research Site
  • Naimuang, Thailand, 30000
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Research Site
  • Ankara, Turkey (Türkiye), 06800
    • Research Site
  • Ankara, Turkey (Türkiye), 06010
    • Research Site
  • Cordaleo, Turkey (Türkiye), 35575
    • Research Site
  • Diyarbakır, Turkey (Türkiye), 21280
    • Research Site
  • Goztepe Istanbul, Turkey (Türkiye)
    • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Research Site
  • Bristol, United Kingdom, BS2 8ED
    • Research Site
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
  • Edinburgh, United Kingdom, EH4 2XR
    • Research Site
  • London, United Kingdom, W6 8RF
    • Research Site
  • London, United Kingdom, NW1 2PG
    • Research Site
  • Middlesbrough, United Kingdom, TS4 3BW
    • Research Site
  • Poole, United Kingdom, BH15 2JB
    • Research Site
  • Torquay, United Kingdom, TQ2 7AA
    • Research Site
  • Truro, United Kingdom, TR1 3LJ
    • Research Site
  • Wolverhampton, United Kingdom, WV10 OQP
    • Research Site
• United States
  • California
    • San Diego, California, United States, 92123
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Research Site
  • Florida
    • Stuart, Florida, United States, 34994
      • Research Site
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Research Site
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Research Site
    • Louisville, Kentucky, United States, 40241
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
    • Baltimore, Maryland, United States, 21201
      • Research Site
    • Baltimore, Maryland, United States, 21229
      • Research Site
    • Bethesda, Maryland, United States, 20817
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Research Site
  • Montana
    • Billings, Montana, United States, 59101
      • Research Site
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Research Site
  • New York
    • Ithaca, New York, United States, 14850
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
    • Cleveland, Ohio, United States, 44124
      • Research Site
    • Maumee, Ohio, United States, 43537
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • York, Pennsylvania, United States, 17403
      • Research Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site
    • Fairfax, Virginia, United States, 22031
      • Research Site
    • Fredericksburg, Virginia, United States, 22408
      • Research Site
    • Richmond, Virginia, United States, 23235
      • Research Site
  • Washington
    • Richland, Washington, United States, 99352
      • Research Site
    • Spokane, Washington, United States, 99204
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site
• Vietnam
  • Haiphong, Vietnam, 180000
    • Research Site
  • Hanoi, Vietnam, 100000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

INCLUSION CRITERIA:

• Participant must be ≥ 18 years at the time of screening.
• Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
• Provision of a tumour tissue sample obtained prior to CRT
• Documented tumour PD-L1 status by central lab
• Documented EGFR and ALK wild-type status (local or central).
• Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
• Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
• 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.
• WHO performance status of 0 or 1 at randomization
• Adequate organ and marrow function

EXCLUSION CRITERIA:

• 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, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
• Mixed small cell and non-small cell lung cancer histology.
• Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
• Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
• Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
• Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
• 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 - diagnosed in the past 6 months prior to randomization.
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Durvalumab and Oleclumab; Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Drug: Oleclumab; Oleclumab IV (intravenous infusion)
Experimental: Arm B: Durvalumab and Monalizumab; Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other: Placebo; Placebo IV (intravenous infusion); Drug: Monalizumab; Monalizumab IV (intravenous infusion)
Active Comparator: Arm C: Durvalumab and Placebo; Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other: Placebo; Placebo IV (intravenous infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Surival (PFS)	Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.	Up to 5 years after first patient randomized.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS)	Up to 9 years after first patient randomized
Objective response rate (ORR)	Objective response rate (ORR) per RECIST 1.1 as assessed by BICR	Up to 5 years after first patient randomized
Overall survival (OS) at 24 months	Overall survival (OS) at 24 months	Up to 9 years after first patient randomized
Duration of response (DoR)	Duration of response (DoR) per RECIST 1.1 as assessed by BICR	Up to 5 years after first patient randomized
Progression free survival (PFS) at 6, 12, 18, and 24 months	Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR	From date of randomization until 24 months
Time from randomization to second progression (PFS2)	Time from randomization to second progression (PFS2)	Up to 5 years after first patient randomized
Time from randomization to first date of distant metastasis or death (TTDM)	Time from randomization to first date of distant metastasis or death (TTDM)	Up to 5 years after first patient randomized
Time from randomization to start date of first subsequent therapy (TFST)	Time from randomization to start date of first subsequent therapy (TFST)	Up to 9 years after first patient randomized
Progression free survival (PFS) as assessed by Investigator	Progression free survival (PFS) as assessed by Investigator	Up to 5 years after first patient randomized
IHC analysis of PD-L1 TC expression	IHC analysis of PD-L1 TC expression relative to efficacy outcomes	Up to 5 years after first patient randomized
Concentration of Durvalumab	To assess the Pharmacokinetics of Durvalumab when in combination with Monalizumab or Oleclumab - serum peak and trough concentrations	From date of randomization until 3 months after date of last IP dose
Anti-drug antibodies (ADAs)	The immunogenicity of durvalumab, oleclumab, and monalizumab as assessed by presence of anti-drug antibodies (ADAs)	From date of randomization until 3 months after date of last IP dose
Time to deterioration in pulmonary symptoms (TTFCD)	Time to deterioration in pulmonary symptoms (TTFCD)	Up to 5 years after last patient randomized
Concentration of Oleclumab	To assess the Pharmacokinetics of Oleclumab when in combination with Durvulumab - serum peak and trough concentrations	From date of randomization until 3 months after last dose of IP
Concentration of Monalizumab	To assess the Pharmacokinetics of Monalizumab when in combination with Durvalumab - serum peak and trough concentrations	From date of randomization until 3 months after last dose of IP

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Fabrice Barlesi, MD, Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

General Publications

• Barlesi F, Cho BC, Goldberg SB, Yoh K, Zimmer Gelatti AC, Mann H, Gopinathan A, Bielecka ZF, Newton M, Aggarwal C. PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer. Future Oncol. 2024;20(29):2137-2147. doi: 10.1080/14796694.2024.2354160. Epub 2024 Jul 18.

Helpful Links

• Lung Cancer Study Locator details

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 2, 2030

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Locally Advanced NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; durvalumab; monalizumab
• Other Study ID Numbers: D9078C00001; 2021-004346-37 (EudraCT Number); 2023-503999-24-00 (Registry Identifier: Clinical Trial Information System (CTIS))

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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• 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