NCT03164616 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS); D + SoC Compared With SoC Alone

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outcome · POSTED

Overall Survival (OS); D + SoC Compared With SoC Alone

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outcome · POSTED

PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC

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outcome · POSTED

OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Best Objective Response (BoR)

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outcome · POSTED

Duration of Response (DoR)

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outcome · POSTED

Time From Randomization to Second Progression (PFS2)

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outcome · POSTED

Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations

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outcome · POSTED

PK of Tremelimumab; Peak and Trough Serum Concentrations

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outcome · POSTED

Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab

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outcome · POSTED

Number of Patients With ADA Response to Tremelimumab

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outcome · POSTED

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)

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outcome · POSTED

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
durvalumab + tremelimumab combination therapy + SoC chemotherapy
intervention Names
Drug: Durvalumab
Drug: Tremelimumab
Drug: Abraxane + carboplatin
Drug: Gemcitabine + cisplatin
Drug: Gemcitabine + carboplatin
Drug: Pemetrexed + carboplatin
Drug: Pemetrexed + cisplatin
label
Treatment Arm 1
type
EXPERIMENTAL
description
durvalumab monotherapy + SoC chemotherapy
intervention Names
Drug: Durvalumab
Drug: Abraxane + carboplatin
Drug: Gemcitabine + cisplatin
Drug: Gemcitabine + carboplatin
Drug: Pemetrexed + carboplatin
Drug: Pemetrexed + cisplatin
label
Treatment Arm 2
type
EXPERIMENTAL
description
SoC chemotherapy alone
intervention Names
Drug: Abraxane + carboplatin
Drug: Gemcitabine + cisplatin
Drug: Gemcitabine + carboplatin
Drug: Pemetrexed + carboplatin
Drug: Pemetrexed + cisplatin
label
Treatment Arm 3
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Treatment Arm 1
Treatment Arm 2
description
IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until disease progression or other discontinuation criteria
name
Durvalumab
type
DRUG
arm Group Labels
Treatment Arm 1
description
IV infusions every 3 weeks for 12 weeks (4 cycles). An additional dose of tremelimumab will be administered in the week 16.
name
Tremelimumab
type
DRUG
arm Group Labels
Treatment Arm 1
Treatment Arm 2
Treatment Arm 3
description
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).
name
Abraxane + carboplatin
type
DRUG
arm Group Labels
Treatment Arm 1
Treatment Arm 2
Treatment Arm 3
description
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).
name
Gemcitabine + cisplatin
type
DRUG
arm Group Labels
Treatment Arm 1
Treatment Arm 2
Treatment Arm 3
description
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).
name
Gemcitabine + carboplatin
type
DRUG
arm Group Labels
Treatment Arm 1
Treatment Arm 2
Treatment Arm 3
description
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.
name
Pemetrexed + carboplatin
type
DRUG
arm Group Labels
Treatment Arm 1
Treatment Arm 2
Treatment Arm 3
description
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.
name
Pemetrexed + cisplatin
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1186
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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).
measure
Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
time Frame
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).
description
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).
measure
Overall Survival (OS); D + SoC Compared With SoC Alone
time Frame
From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

secondary Outcomes

description
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.
measure
PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
time Frame
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.
description
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.
measure
OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
time Frame
From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
description
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.
measure
Objective Response Rate (ORR)
time Frame
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).
description
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.
measure
Best Objective Response (BoR)
time Frame
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).
description
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.
measure
Duration of Response (DoR)
time Frame
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).
description
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.
measure
Time From Randomization to Second Progression (PFS2)
time Frame
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).
description
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.
measure
Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
time Frame
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.
description
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.
measure
PK of Tremelimumab; Peak and Trough Serum Concentrations
time Frame
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.
description
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.
measure
Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
time Frame
Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).
description
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.
measure
Number of Patients With ADA Response to Tremelimumab
time Frame
Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).
description
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.
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)
time Frame
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).
description
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.
measure
Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)
time Frame
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).

Full study description

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.

Source references

references

citation
Peters S, Cho BC, Luft AV, Alatorre-Alexander J, Geater SL, Laktionov K, Trukhin D, Kim SW, Ursol GM, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Lowery C, Mann H, Stewart R, Jiang H, Garon EB, Mok T, Johnson ML. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes From the Phase 3 POSEIDON Trial. J Thorac Oncol. 2025 Jan;20(1):76-93. doi: 10.1016/j.jtho.2024.09.1381. Epub 2024 Sep 5.
pmid
39243945
type
DERIVED
citation
He JZ, Duval V, Jauslin P, Goncalves A, Abegesah A, Fan C, Lim K, Song X, Chen C, Shi X, Mann H, Krug L, Ren S, Phipps A, Gibbs M, Zhou D. Population Pharmacokinetics and Exposure-Response Analysis for the CTLA-4 Inhibitor Tremelimumab in Metastatic NSCLC Patients in the Phase III POSEIDON Study. Clin Pharmacol Ther. 2023 Dec;114(6):1375-1386. doi: 10.1002/cpt.3063. Epub 2023 Oct 17.
pmid
37777827
type
DERIVED
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.
pmid
36327426
type
DERIVED