Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). (POSEIDON)

A Phase III, Randomized, Multi-Center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Patients With Metastatic Non Small-Cell Lung Cancer (NSCLC) (POSEIDON)

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy + Standard of care (SoC) chemotherapy or durvalumab monotherapy + SoC chemotherapy versus SoC chemotherapy alone as first line treatment in patients with metastatic non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer NSCLC
• Intervention / Treatment: Drug: Durvalumab; Drug: Tremelimumab; Drug: Abraxane + carboplatin; Drug: Gemcitabine + cisplatin; Drug: Gemcitabine + carboplatin; Drug: Pemetrexed + carboplatin; Drug: Pemetrexed + cisplatin

Detailed Description

Adult patients with a histologically or cytologically documented metastatic NSCLC, with tumors that lack activating EGFR mutations and ALK fusions, are eligible for enrollment. Patients will be randomized in a 1:1:1 ratio to receive treatment with durvalumab + tremelimumab combination therapy + SoC chemotherapy, durvalumab monotherapy + SoC chemotherapy, or SoC chemotherapy alone. Tumor evaluation scans will be performed until objective disease progression as efficacy assessment. All patients will be followed for survival until the end of the study. An independent data monitoring committee (IDMC) composed of independent experts will be convened to confirm the safety and tolerability of the proposed dose and schedule.

• Study Type: Interventional
• Enrollment (Actual): 1186
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Belo Horizonte, Brazil, 30380-472
    • Research Site
  • Curitiba, Brazil, 81520-060
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 90610-000
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  • Porto Alegre, Brazil, 91350-200
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  • Ribeirao Preto, Brazil, 14015-140
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
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  • Santo Andre, Brazil, 09080-110
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  • Santo André, Brazil, 09060-650
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  • Sao Paulo, Brazil, 01209-000
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  • São José do Rio Preto, Brazil, 15090-000
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  • São Paulo, Brazil, 03102-002
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  • São Paulo, Brazil, 01246-000
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• Bulgaria
  • Plovdiv, Bulgaria, 4000
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  • Plovdiv, Bulgaria, 4004
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  • Sofia, Bulgaria, 1431
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  • Sofia, Bulgaria, 1784
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  • Sofia, Bulgaria, 1330
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  • Sofia, Bulgaria, 1618
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  • Varna, Bulgaria, 9010
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• China
  • Beijing, China, 100142
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  • Beijing, China, 100021
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  • Changchun, China, 130012
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  • Changsha, China, 410013
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  • Fuzhou, China, 350014
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  • Guangzhou, China, 510080
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  • Hangzhou, China, 310022
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  • Harbin, China, 150081
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  • Hefei, China, 230601
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  • Kunming, China, CN-650034
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  • Linyi, China, 276000
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  • Liuzhou, China, 545006
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  • Nanjing, China, 210009
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  • Qingdao, China, 110016
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  • Shanghai, China, 200032
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  • Shanghai, China, 200080
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  • Shanghai, China, 200030
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  • Shantou, China, 515041
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  • Wuhan, China, 430079
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  • Wuhan, China, 430022
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  • Xining, China, 810001
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  • Yangzhou, China, 225001
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  • Zhanjiang, China, 524001
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  • Zhengzhou, China, 450008
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  • Zhengzhou, China, 450052
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• Germany
  • Berlin, Germany, 13125
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  • Essen, Germany, 45122
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  • Freiburg, Germany, 79106
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  • Gauting, Germany, 82131
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  • Hamburg, Germany, 21075
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  • Hamburg, Germany, 20251
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  • Heidelberg, Germany, 69126
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  • Immenhausen, Germany, 34376
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  • Mainz, Germany, 55131
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  • Oldenburg, Germany, 26121
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  • Würzburg, Germany, 97067
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• Hong Kong
  • Shatin, Hong Kong, 00000
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• Hungary
  • Budapest, Hungary, 1083
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  • Budapest, Hungary, 1121
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  • Kecskemét, Hungary, 6000
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  • Miskolc, Hungary, 3529
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  • Törökbálint, Hungary, 2045
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• Japan
  • Bunkyo-ku, Japan, 113-8603
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  • Chuo-ku, Japan, 104-0045
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  • Fukuoka-shi, Japan, 812-8582
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  • Hiroshima-shi, Japan, 730-0011
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  • Iwakuni-shi, Japan, 740-8510
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  • Kanazawa, Japan, 920-8641
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  • Kashiwa, Japan, 227-8577
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  • Koto-ku, Japan, 135-8550
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  • Kurume-shi, Japan, 830-0011
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  • Matsuyama-shi, Japan, 790-0007
    • Research Site
  • Okayama-shi, Japan, 700-8558
    • Research Site
  • Okayama-shi, Japan, 700-8607
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  • Osakasayama, Japan, 589-8511
    • Research Site
  • Sapporo-shi, Japan, 003-0804
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  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Toyoake-shi, Japan, 470-1101
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  • Ube-shi, Japan, 755-0241
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  • Yokohama-shi, Japan, 241-8515
    • Research Site
  • Yokohama-shi, Japan, 236-0004
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Research Site
  • Chungcheongbuk-do, Korea, Republic of, 28644
    • Research Site
  • Daegu, Korea, Republic of, 42415
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
  • Seoul, Korea, Republic of, 6351
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  • Seoul, Korea, Republic of, 120-752
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  • Ulsan, Korea, Republic of, 44033
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• Mexico
  • Aguascalientes, Mexico, 20230
    • Research Site
  • Cuautitlan Izcalli, Mexico, 54769
    • Research Site
  • Guadalajara, Mexico, 44280
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  • Mexico, Mexico, 14080
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  • Mexico City, Mexico, 0 3100
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • Monterrey, Mexico, 64060
    • Research Site
  • México, Mexico, 04739
    • Research Site
  • Tuxtla, Mexico, 29030
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• Peru
  • Arequipa, Peru, AREQUIPA01
    • Research Site
  • Lima, Peru, L27
    • Research Site
  • Lima, Peru, LIMA 34
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  • Lima, Peru, LIMA 41
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  • Lima, Peru, LIMA 29
    • Research Site
  • San Isidro, Peru, 27
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• Poland
  • Olsztyn, Poland, 10-357
    • Research Site
  • Tomaszów Mazowiecki, Poland, 97-200
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  • Warszawa, Poland, 02-781
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  • Wodzisław Śląski, Poland, 44-300
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 125367
    • Research Site
  • Moscow, Russian Federation, 105229
    • Research Site
  • Moscow, Russian Federation, 115280
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  • Omsk, Russian Federation, 644013
    • Research Site
  • Saint Petersburg, Russian Federation, 195271
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  • Saint-Petersburg, Russian Federation, 194291
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  • Sankt-Peterburg, Russian Federation, 196603
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  • St. Petersburg, Russian Federation, 197758
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• South Africa
  • Durban, South Africa, 4091
    • Research Site
  • Johannesburg, South Africa, 0001
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  • Kraaifontein, South Africa, 7570
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  • Parktown, South Africa, 2193
    • Research Site
  • Pretoria, South Africa, 0001
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  • Rondebosch, South Africa, 7700
    • Research Site
  • Vereeniging, South Africa, 1930
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• Taiwan
  • Changhua City, Taiwan, 50006
    • Research Site
  • Kaohsiung, Taiwan, 82445
    • Research Site
  • Kaohsiung City, Taiwan, 83301
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 112
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  • Tao-Yuan, Taiwan, 333
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• Thailand
  • Bangkok, Thailand, 10210
    • Research Site
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Muang, Thailand, 50200
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  • Songkhla, Thailand, 90110
    • Research Site
• Ukraine
  • Dnipro, Ukraine, 49102
    • Research Site
  • Ivano-Frankivsk, Ukraine, 76018
    • Research Site
  • Kirovohrad, Ukraine, 25006
    • Research Site
  • Kyiv, Ukraine, 03115
    • Research Site
  • Kyiv, Ukraine, 03022
    • Research Site
  • Lviv, Ukraine, 79031
    • Research Site
  • Odesa, Ukraine, 65055
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  • Sumy, Ukraine, 40022
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  • Vinnytsia, Ukraine, 21029
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  • Zaporizhzhia, Ukraine, 69040
    • Research Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Research Site
  • London, United Kingdom, W6 8RF
    • Research Site
  • London, United Kingdom, NW1 2PG
    • Research Site
  • London, United Kingdom, EC1M 6BQ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Research Site
  • California
    • Bakersfield, California, United States, 93309
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Research Site
    • Jacksonville, Florida, United States, 32224
      • Research Site
    • Saint Petersburg, Florida, United States, 33705
      • Research Site
    • West Palm Beach, Florida, United States, 33401
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Site
  • Ohio
    • Canton, Ohio, United States, 44710
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Research Site
    • Houston, Texas, United States, 77090
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • 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:

For inclusion in the study, patients should fulfill the following criteria:

1. Aged at least 18 years.
2. Histologically or cytologically documented Stage IV NSCLC.
3. Confirmed tumor PD-L1 status prior to randomization.
4. Patients must have tumors that lack activating EGFR mutations and ALK fusions.
5. No prior chemotherapy or any other systemic therapy for metastatic NSCLC.
6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. No prior exposure to immunemediated therapy, excluding therapeutic anticancer vaccines.

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant.
2. Active or prior documented autoimmune or inflammatory disorders.
3. Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids.
4. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm 1; durvalumab + tremelimumab combination therapy + SoC chemotherapy	Drug: Durvalumab; IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until disease progression or other discontinuation criteria; Drug: Tremelimumab; IV infusions every 3 weeks for 12 weeks (4 cycles). An additional dose of tremelimumab will be administered in the week 16.; Drug: Abraxane + carboplatin; Standard of care chemotherapy (squamous and non-squamous patients): Abraxane 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Carboplatin Area under the plasma drug concentration-time curve (AUC) 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Gemcitabine + cisplatin; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Gemcitabine + carboplatin; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Pemetrexed + carboplatin; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.; Drug: Pemetrexed + cisplatin; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.
Experimental: Treatment Arm 2; durvalumab monotherapy + SoC chemotherapy	Drug: Durvalumab; IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until disease progression or other discontinuation criteria; Drug: Abraxane + carboplatin; Standard of care chemotherapy (squamous and non-squamous patients): Abraxane 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Carboplatin Area under the plasma drug concentration-time curve (AUC) 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Gemcitabine + cisplatin; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Gemcitabine + carboplatin; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Pemetrexed + carboplatin; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.; Drug: Pemetrexed + cisplatin; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.
Active Comparator: Treatment Arm 3; SoC chemotherapy alone	Drug: Abraxane + carboplatin; Standard of care chemotherapy (squamous and non-squamous patients): Abraxane 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Carboplatin Area under the plasma drug concentration-time curve (AUC) 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Gemcitabine + cisplatin; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Gemcitabine + carboplatin; Standard of care chemotherapy (squamous patients only): Gemcitabine 1000 or 1250 mg/m2 via IV infusion on Days 1 and 8 of each 21-day cycle + carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3).; Drug: Pemetrexed + carboplatin; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 21-day cycle for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.; Drug: Pemetrexed + cisplatin; Standard of care chemotherapy (non-squamous patients only): Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 via IV infusion on Day 1 of each 21-day cycle, for 4 to 6 cycles (ie, 4 cycles for Treatment Arms 1 and 2 and 4 to 6 cycles for Treatment Arm 3); then continue pemetrexed 500 mg/m2 maintenance [i.e., q4w for Treatment Arms 1 and 2. For Treatment Arm 3, Pemetrexed maintenance therapy can be given either q3w or q4w (dependent on Investigator decision and local standards)] until objective disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS); D + SoC Compared With SoC Alone	PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity).	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Overall Survival (OS); D + SoC Compared With SoC Alone	OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity).	From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC	PFS (per RECIST 1.1 using BICR assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique.	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months.
OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC	OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.	From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
Objective Response Rate (ORR)	ORR (per RECIST 1.1 using BICR assessments) was defined as the percentage of patients with at least one visit response of complete response (CR) or partial response (PR). Results are presented for the pre-specified ORR analysis using unconfirmed responses based on BICR.	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Best Objective Response (BoR)	The BoR was calculated based on the overall visit responses from each RECIST 1.1 assessment. BOR was defined as the best response a patient had following randomization, but prior to starting any subsequent cancer therapy and up to and including RECIST 1.1 progression or the last evaluable assessment in the absence of RECIST 1.1 progression, as determined by BICR. Categorization of BoR was based on RECIST using the following 'response' categories: CR and PR and the following 'non-response' categories: stable disease (SD) ≥6 weeks, progression (ie, PD) and not evaluable (NE). Results are presented for number (%) of patients in each specified category.	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Duration of Response (DoR)	DoR (per RECIST 1.1 using BICR assessments) was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response coincided with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint. The time of the initial response was defined as the latest of the dates contributing towards the first visit of PR or CR. Results are presented for the pre-specified DoR analysis using unconfirmed responses based on BICR.	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Time From Randomization to Second Progression (PFS2)	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) or death. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of: objective radiological imaging, symptomatic progression or death.	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations	To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.	Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.
PK of Tremelimumab; Peak and Trough Serum Concentrations	To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.	Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.
Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab	Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against durvalumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples.	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).
Number of Patients With ADA Response to Tremelimumab	Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against tremelimumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples.	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).
Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)	The EORTC QLQ-Core 30 version 3 (QLQ-C30 v3) was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)	The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Xiaojin Shi, M.D., MSc, One MedImmune Way, Gaithersburg, Maryland 20878, United States

Publications and helpful links

General Publications

• Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, Kim SW, Ursol G, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Shi X, Poole L, Peters S, Garon EB, Mok T; POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. doi: 10.1200/JCO.22.00975. Epub 2022 Nov 3.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): March 12, 2021
• Study Completion (Estimated): May 28, 2025

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: May 22, 2017
• First Posted (Actual): May 23, 2017

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Durvalumab; Tremelimumab; Progression-free survival (PFS); Programmed cell death ligand 1 (PD-L1); Overall survival (OS)
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Cisplatin; Durvalumab; Tremelimumab; Albumin-Bound Paclitaxel; Pemetrexed; Gemcitabine
• Other Study ID Numbers: D419MC00004; 2017-000920-81 (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 refer 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