A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC)

A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients With Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)

A Global Study to Assess the Effects of MEDI4736 following concurrent chemoradiation in Patients with Stage III Unresectable Non-Small Cell Lung Cancer.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: MEDI4736; Other: PLACEBO

Detailed Description

A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)

• Study Type: Interventional
• Enrollment (Actual): 713
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Research Site
  • Bendigo, Australia, 3550
    • Research Site
  • Box Hill, Australia, 3128
    • Research Site
  • Clayton, Australia, 3168
    • Research Site
  • Heidelberg, Australia, 3084
    • Research Site
  • Herston, Australia, 4029
    • Research Site
  • Kogarah, Australia, 2217
    • Research Site
  • Launceston, Australia, 7250
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Port Macquarie, Australia, 2444
    • Research Site
  • Randwick, Australia, 2031
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
  • Woolloongabba, Australia, 4102
    • Research Site
• Belgium
  • Aalst, Belgium, 9300
    • Research Site
  • Gilly, Belgium, 6060
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Libramont-Chevigny, Belgium, 6800
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Canada
  • Toronto, Canada, M5G 2M9
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Research Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Research Site
    • London, Ontario, Canada, N6A 4L6
      • Research Site
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Research Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
• Chile
  • Santiago, Chile, 7500000
    • Research Site
  • Santiago, Chile, 8420383
    • Research Site
  • Viña del Mar, Chile
    • Research Site
• France
  • Avignon Cedex 9, France, 84918
    • Research Site
  • Bayonne, France, 64100
    • Research Site
  • Brest Cedex, France, 29609
    • Research Site
  • Lille, France, 59037
    • Research Site
  • Lyon, France, 69008
    • Research Site
  • Marseille Cedex 20, France, 13915
    • Research Site
  • Montpellier Cedex, France, 34295
    • Research Site
  • Nantes, France, 44202
    • Research Site
  • Nice, France, 06100
    • Research Site
  • Pau cedex, France, 6400
    • Research Site
  • Rennes, France, 35033
    • Research Site
  • Saint Herblain, France, 44805
    • Research Site
  • Toulouse, France, 31000
    • Research Site
  • Villejuif Cedex, France, 94805
    • Research Site
• Germany
  • Berlin, Germany, 12351
    • Research Site
  • Berlin, Germany, 10967
    • Research Site
  • Esslingen, Germany, 73730
    • Research Site
  • Grosshansdorf, Germany, 20927
    • Research Site
  • Hamburg, Germany, 20251
    • Research Site
  • Hamburg, Germany, 22081
    • Research Site
  • Löwenstein, Germany, 74245
    • Research Site
  • Recklinghausen, Germany, 45659
    • Research Site
  • Regensburg, Germany, 93053
    • Research Site
  • Villingen-Schwenningen, Germany, 78052
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Heraklion, Greece, 71110
    • Research Site
  • Patras, Greece, 26500
    • Research Site
  • Thessaloniki, Greece, 57010
    • Research Site
  • Thessaloniki, Greece, 54645
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Budapest, Hungary, 1121
    • Research Site
  • Gyula, Hungary, 5703
    • Research Site
  • Miskolc, Hungary, 3529
    • Research Site
• Israel
  • Haifa, Israel, 31096
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
• Italy
  • Aviano, Italy, 33081
    • Research Site
  • Catania, Italy, 95123
    • Research Site
  • Cremona, Italy, 26100
    • Research Site
  • Lecce, Italy, 73100
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Napoli, Italy, 80138
    • Research Site
  • Pisa, Italy, 56126
    • Research Site
  • Roma, Italy, 00144
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8603
    • Research Site
  • Bunkyo-ku, Japan, 113-8431
    • Research Site
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Fukuoka, Japan, 812-8582
    • Research Site
  • Habikino-shi, Japan, 583-8588
    • Research Site
  • Hidaka-shi, Japan, 350-1298
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Research Site
  • Hiroshima-shi, Japan, 730-8518
    • Research Site
  • Kanazawa, Japan, 920-8641
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Kitaadachi-gun, Japan, 362-0806
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site
  • Nagoya-shi, Japan, 460-0001
    • Research Site
  • Natori-shi, Japan, 981-1293
    • Research Site
  • Okayama-shi, Japan, 700-8558
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Osakasayama, Japan, 589-8511
    • Research Site
  • Ota-shi, Japan, 373-8550
    • Research Site
  • Sagamihara-shi, Japan, 252-0375
    • Research Site
  • Sakai-shi, Japan, 591-8555
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Takatsuki-shi, Japan, 569-8686
    • Research Site
  • Ube-shi, Japan, 755-0241
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
  • Yokohama-shi, Japan, 236-0051
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Research Site
  • Cheongju-si, Korea, Republic of, 361-711
    • Research Site
  • Hwasun-gun, Korea, Republic of, 58128
    • Research Site
  • Incheon, Korea, Republic of, UNK
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Suwon, Korea, Republic of, 16247
    • Research Site
• Mexico
  • Cuautitlan Izcalli, Mexico, 54769
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • Oaxaca, Mexico, 68000
    • Research Site
  • Orizaba, Mexico, 94300
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Amsterdam, Netherlands, 1081 HV
    • Research Site
  • Breda, Netherlands, 4818 CK
    • Research Site
  • Eindhoven, Netherlands, 5623EJ
    • Research Site
  • Rotterdam, Netherlands, 3015 CE
    • Research Site
  • Tilburg, Netherlands, 5022 GC
    • Research Site
• Peru
  • Lima, Peru, LIMA 27
    • Research Site
  • Lima, Peru, 41
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Lublin, Poland, 20-362
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Singapore
  • Singapore, Singapore, 169610
    • Research Site
  • Singapore, Singapore, 308433
    • Research Site
  • Singapore, Singapore, 119074
    • Research Site
• Slovakia
  • Bardejov, Slovakia, 08501
    • Research Site
  • Kosice, Slovakia, 041 91
    • Research Site
  • Nove Zamky, Slovakia, 94002
    • Research Site
  • Trnava, Slovakia, 91775
    • Research Site
• South Africa
  • Cape Town, South Africa, 7570
    • Research Site
  • Pretoria, South Africa, 0181
    • Research Site
  • Vereeniging, South Africa, 1930
    • Research Site
• Spain
  • Alicante, Spain, 03010
    • Research Site
  • Barcelona, Spain, 08041
    • Research Site
  • Barcelona, Spain, 08003
    • Research Site
  • Barcelona, Spain, 08908
    • Research Site
  • Gerona, Spain, 17007
    • Research Site
  • Lérida, Spain, 25198
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28050
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Madrid, Spain, 28005
    • Research Site
  • San Sebastian, Spain, 20014
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
  • Valencia, Spain, 46014
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taipei, Taiwan, 23561
    • Research Site
  • Taipei City, Taiwan, 110
    • Research Site
• Thailand
  • Bangkok, Thailand, 10400
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
• Turkey
  • Adana, Turkey, 01130
    • Research Site
  • Ankara, Turkey, 06490
    • Research Site
  • Istanbul, Turkey, 34030
    • Research Site
  • Istanbul, Turkey, 34844
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
  • Konya, Turkey, 42080
    • Research Site
  • Malatya, Turkey, 44280
    • Research Site
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Truro, United Kingdom, TR1 3LJ
    • Research Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Research Site
    • Goodyear, Arizona, United States, 85338
      • Research Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72405
      • Research Site
    • Springdale, Arkansas, United States, 72762
      • Research Site
  • California
    • Fullerton, California, United States, 92835
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
    • Oxnard, California, United States, 93030
      • Research Site
    • Sacramento, California, United States, 95816
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Research Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Research Site
    • Jacksonville, Florida, United States, 32207
      • Research Site
    • Miami Beach, Florida, United States, 33140
      • Research Site
    • Orlando, Florida, United States, 32804
      • Research Site
    • Port Saint Lucie, Florida, United States, 34952
      • Research Site
    • Saint Petersburg, Florida, United States, 33705
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Research Site
    • Atlanta, Georgia, United States, 30322
      • Research Site
    • Fort Gordon, Georgia, United States, 30905
      • Research Site
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
    • Marietta, Georgia, United States, 30060
      • Research Site
  • Iowa
    • Waterloo, Iowa, United States, 50701
      • Research Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Research Site
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
    • Rockville, Maryland, United States, 20850
      • Research Site
    • Rosedale, Maryland, United States, 21237
      • Research Site
    • Salisbury, Maryland, United States, 21801
      • Research Site
    • Towson, Maryland, United States, 21204
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55426
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Research Site
  • New York
    • Bronx, New York, United States, 10461
      • Research Site
    • Lake Success, New York, United States, 11041
      • Research Site
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Research Site
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Pinehurst, North Carolina, United States, 28374
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Ohio
    • Blue Ash, Ohio, United States, 45242
      • Research Site
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
    • Nashville, Tennessee, United States, 37232-8805
      • Research Site
  • Texas
    • Austin, Texas, United States, 78731
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Fort Worth, Texas, United States, 76104
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • Tyler, Texas, United States, 75702
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site
  • Washington
    • Spokane, Washington, United States, 99208
      • Research Site
    • Spokane, Washington, United States, 99218
      • Research Site
    • Vancouver, Washington, United States, 98684
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh, 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

Inclusion Criteria:

1. Age at least 18 years.
2. Documented evidence of NSCLC (locally advanced, unresectable, Stage III)
3. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.
4. World Health Organisation (WHO) Performance Status of 0 to 1.
5. Estimated life expectancy of more than 12 weeks.

Exclusion Criteria:

1. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
2. Active or prior autoimmune disease or history of immunodeficiency.
3. Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
4. Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy.
6. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI4736; MEDI4736 (intravenous infusion)	Drug: MEDI4736; MEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier . The 2:1 ratio (MEDI4736 to placebo).
Placebo Comparator: PLACEBO; Placebo (matching placebo for intravenous infusion)	Other: PLACEBO; PLACEBO by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier . The 2:1 ratio (MEDI4736 to placebo).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique.	Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Overall Survival	OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique.	From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1	ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.	Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1	DoR was defined as the time from date for first documented response of CR or PR until the first documented response of progression per RECIST 1.1 or death in the absence of progression. DoR was calculated using the Kaplan-Meier technique.	Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1	APF12 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months.	Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1	APF18 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of PFS at 18 months.	Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1	TTDM 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 of the radiation field according to RECIST 1.1 or proven by biopsy. TTDM was calculated using the Kaplan-Meier technique.	Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Percentage of Patients Alive at 24 Months (OS24)	OS24 was defined as the percentage of patients who were alive at 24 months after randomization per the Kaplan-Meier estimate of OS at 24 months.	From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Time to Second Progression or Death (PFS2)	PFS2 was defined as the time from randomization to the time of the second progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could have involved any of the following: objective radiological, symptomatic progression, or death. RECIST assessments were not collected for assessment of PFS2. PFS2 was calculated using the Kaplan-Meier technique.	Following confirmed progression, patients were assessed every ~12 weeks until second disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL), Assessed Using European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30)	Global health status/HRQoL was assessed using the EORTC QLQ-C30 global QoL scale which includes 2 items from the QLQ-C30: "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall QoL during the past week?" (Item 30). Scores from 0 to 100 were derived for each item with higher scores indicating a better health status. Time to deterioration for global health status/HRQoL was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in global health status/HRQoL from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful deterioration. Time to deterioration was calculated using the Kaplan-Meier technique.	At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Time to Deterioration of Primary Patient-Reported Outcome (PRO) Symptoms, Assessed Using European Organization for Research and Treatment of Cancer QoL Lung Cancer Module (EORTC QLQ-LC13)	The EORTC QLQ-LC13 is a lung cancer specific module from the EORTC comprising 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, chest pain, arm/shoulder pain, and other pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. Scores from 0 to 100 were derived for each symptom item with higher scores representing greater symptom severity. Time to symptom deterioration was defined as time from randomization until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration. Results are presented for time to deterioration in the following PRO endpoints identified as primary for EORTC QLQ-LC13: dyspnea, cough, hemoptysis and chest pain. Time to deterioration was calculated using the Kaplan-Meier technique.	At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.
Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations	To evaluate PK, blood samples were collected pre-dose and post-dose and trough and peak serum concentrations of durvalumab, respectively, were determined. Pre-dose samples were taken within 60 minutes before infusion and post-dose samples were taken within 10 minutes after the end of infusion.	Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48, and post-dose on Day 1 (Week 0) and Week 24. Analysis performed at 22 Mar 2018 DCO.
Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab	ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted by ≥4-fold following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Confirmed ADA positive samples were subsequently tested in a neutralizing antibody assay.	Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48. Analysis performed at 22 Mar 2018 DCO.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Phil Dennis, MD, AstraZeneca

Publications and helpful links

General Publications

• Senan S, Ozguroglu M, Daniel D, Villegas A, Vicente D, Murakami S, Hui R, Faivre-Finn C, Paz-Ares L, Wu YL, Mann H, Dennis PA, Antonia SJ. Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial. ESMO Open. 2022 Apr;7(2):100410. doi: 10.1016/j.esmoop.2022.100410. Epub 2022 Mar 2.
• Naidoo J, Vansteenkiste JF, Faivre-Finn C, Ozguroglu M, Murakami S, Hui R, Quantin X, Broadhurst H, Newton M, Thiyagarajah P, Antonia SJ. Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Lung Cancer. 2022 Apr;166:84-93. doi: 10.1016/j.lungcan.2022.02.003. Epub 2022 Feb 9.
• Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2. Erratum In: J Clin Oncol. 2022 Jun 10;40(17):1965.
• Ouwens M, Darilay A, Zhang Y, Mukhopadhyay P, Mann H, Ryan J, Dennis PA. Assessing the Influence of Subsequent Immunotherapy on Overall Survival in Patients with Unresectable Stage III Non-Small Cell Lung Cancer from the PACIFIC Study. Curr Ther Res Clin Exp. 2021 Aug 12;95:100640. doi: 10.1016/j.curtheres.2021.100640. eCollection 2021.
• Socinski MA, Ozguroglu M, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Gray JE, Park K, Vincent M, Mann H, Newton M, Dennis PA, Antonia SJ. Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Stage III Non-Small-Cell Lung Cancer (PACIFIC). Clin Lung Cancer. 2021 Nov;22(6):549-561. doi: 10.1016/j.cllc.2021.05.009. Epub 2021 Jun 12.
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Helpful Links

• AstraZeneca Cancer Study Locator Service astrazeneca@emergingmed.com 1-877-400-465
• CSR redacted synopsis

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2014
• Primary Completion (Actual): February 13, 2017
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: April 25, 2014
• First Submitted That Met QC Criteria: April 25, 2014
• First Posted (Estimated): April 29, 2014

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Chemoradiation; PD-L1; Locally advanced; Stage III Non-Small Cell Lung Cancer; Unresectable Non-Small Cell Lung Cancer; MEDI4736; Immune-mediated cancer therapy
• 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: D4191C00001; 2014-000336-42 (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. 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 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 deidentified 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