Clinical trial NCT03164616: Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer NSCLC
Keywords: NSCLC
Programmed cell death ligand 1 (PD-L1)
Durvalumab
Tremelimumab
Progression-free survival (PFS)
Overall survival (OS)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2017-05-23
Enrollment: 1186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
timeFrame: 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).
measure: Overall Survival (OS); D + SoC Compared With SoC Alone
timeFrame: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
Secondary outcomes:
measure: PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
timeFrame: 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.
measure: OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
timeFrame: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
measure: Objective Response Rate (ORR)
timeFrame: 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).
measure: Best Objective Response (BoR)
timeFrame: 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).
measure: Duration of Response (DoR)
timeFrame: 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).
measure: Time From Randomization to Second Progression (PFS2)
timeFrame: 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).
measure: Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
timeFrame: 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.
measure: PK of Tremelimumab; Peak and Trough Serum Concentrations
timeFrame: 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.
measure: Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
timeFrame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).
measure: Number of Patients With ADA Response to Tremelimumab
timeFrame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).
measure: 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)
timeFrame: 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).
measure: Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)
timeFrame: 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).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Bakersfield
country: United States
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state: California
city: Santa Monica
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state: California
city: Fort Myers
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city: Jacksonville
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state: Virginia
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country: Brazil
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country: Bulgaria
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city: Beijing
country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: Germany
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country: Germany
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country: Germany
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country: Japan
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country: Japan
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country: Japan
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Mexico
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country: Poland
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country: Poland
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country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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city: St. Petersburg
country: Russian Federation
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country: South Africa
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country: South Africa
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country: South Africa
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country: South Africa
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country: South Africa
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country: South Africa
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country: South Africa
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city: Changhua City
country: Taiwan
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city: Kaohsiung City
country: Taiwan
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country: Taiwan
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country: Taiwan
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country: Taiwan
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country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
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city: Tao-Yuan
country: Taiwan
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city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
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city: Bangkok
country: Thailand
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city: Muang
country: Thailand
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city: Songkhla
country: Thailand
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kirovohrad
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: One MedImmune Way, Gaithersburg, Maryland 20878, United States
name: Xiaojin Shi, M.D., MSc
role: STUDY_DIRECTOR
References:
citation: 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.