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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- AstraZeneca
- Enrollment
- 1,186
- Locations
- 175
- Primary Endpoint
- Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 130 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •For inclusion in the study, patients should fulfill the following criteria:
- •Aged at least 18 years.
- •Histologically or cytologically documented Stage IV NSCLC.
- •Confirmed tumor PD-L1 status prior to randomization.
- •Patients must have tumors that lack activating EGFR mutations and ALK fusions.
- •No prior chemotherapy or any other systemic therapy for metastatic NSCLC.
- •World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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:
- •Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant.
- •Active or prior documented autoimmune or inflammatory disorders.
- •Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids.
- •Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
Arms & Interventions
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Durvalumab (Drug)
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Tremelimumab (Drug)
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Abraxane + carboplatin (Drug)
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Gemcitabine + cisplatin (Drug)
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Gemcitabine + carboplatin (Drug)
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Pemetrexed + carboplatin (Drug)
Treatment Arm 1
durvalumab + tremelimumab combination therapy + SoC chemotherapy
Intervention: Pemetrexed + cisplatin (Drug)
Treatment Arm 2
durvalumab monotherapy + SoC chemotherapy
Intervention: Durvalumab (Drug)
Treatment Arm 2
durvalumab monotherapy + SoC chemotherapy
Intervention: Abraxane + carboplatin (Drug)
Treatment Arm 2
durvalumab monotherapy + SoC chemotherapy
Intervention: Gemcitabine + cisplatin (Drug)
Treatment Arm 2
durvalumab monotherapy + SoC chemotherapy
Intervention: Gemcitabine + carboplatin (Drug)
Treatment Arm 2
durvalumab monotherapy + SoC chemotherapy
Intervention: Pemetrexed + carboplatin (Drug)
Treatment Arm 2
durvalumab monotherapy + SoC chemotherapy
Intervention: Pemetrexed + cisplatin (Drug)
Treatment Arm 3
SoC chemotherapy alone
Intervention: Abraxane + carboplatin (Drug)
Treatment Arm 3
SoC chemotherapy alone
Intervention: Gemcitabine + cisplatin (Drug)
Treatment Arm 3
SoC chemotherapy alone
Intervention: Gemcitabine + carboplatin (Drug)
Treatment Arm 3
SoC chemotherapy alone
Intervention: Pemetrexed + carboplatin (Drug)
Treatment Arm 3
SoC chemotherapy alone
Intervention: Pemetrexed + cisplatin (Drug)
Outcomes
Primary Outcomes
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).
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).
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).
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).
Secondary Outcomes
- Objective Response Rate (ORR)(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).)
- PK of Tremelimumab; Peak and Trough Serum Concentrations(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 ADA Response to Tremelimumab(Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).)
- PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC(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(From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).)
- Best Objective Response (BoR)(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 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)(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).)
- Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations(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.)
- Duration of Response (DoR)(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)(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).)
- Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab(Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).)
- Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)(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).)