Description:
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.
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
D419MC00004
- NCT ID:
NCT03164616
Conditions
- Non Small Cell Lung Cancer NSCLC
Interventions
| Drug | Synonyms | Arms |
|---|
| Durvalumab | | Treatment Arm 1 |
| Tremelimumab | | Treatment Arm 1 |
| Abraxane + carboplatin | | Treatment Arm 1 |
| Gemcitabine + cisplatin | | Treatment Arm 1 |
| Gemcitabine + carboplatin | | Treatment Arm 1 |
| Pemetrexed + carboplatin | | Treatment Arm 1 |
| Pemetrexed + cisplatin | | Treatment Arm 1 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Treatment Arm 1 | Experimental | durvalumab + tremelimumab combination therapy + SoC chemotherapy | - Durvalumab
- Tremelimumab
- Abraxane + carboplatin
- Gemcitabine + cisplatin
- Gemcitabine + carboplatin
- Pemetrexed + carboplatin
- Pemetrexed + cisplatin
|
| Treatment Arm 2 | Experimental | durvalumab monotherapy + SoC chemotherapy | - Durvalumab
- Abraxane + carboplatin
- Gemcitabine + cisplatin
- Gemcitabine + carboplatin
- Pemetrexed + carboplatin
- Pemetrexed + cisplatin
|
| Treatment Arm 3 | Active Comparator | SoC chemotherapy alone | - Abraxane + carboplatin
- Gemcitabine + cisplatin
- Gemcitabine + carboplatin
- Pemetrexed + carboplatin
- Pemetrexed + cisplatin
|
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.
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival (PFS) using Blinded Independent Central Review (BICR) assessments according to RECIST 1.1 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Progression-free survival (PFS) using BICR assessments according to RECIST 1.1 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Overall survival (OS) |
| Time Frame: | Up to 4 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Objective response rate (ORR) using BICR assessments according to RECIST 1.1 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response (DoR) using BICR assessments according to RECIST 1.1 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Time from randomization to second progression (PFS2) |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of patients alive and progression free at 12 months from randomization (APF12) using BICR assessments according to RECIST 1.1 |
| Time Frame: | Up to 12 months |
| Safety Issue: | |
| Description: | |
| Measure: | Best objective response (BoR) using BICR assessments according to RECIST 1.1 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by concentration |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | The immunogenicity of durvalumab and tremelimumab as assessed by presence of anti-drug antibodies (ADAs) |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Health-related QoL measured by EORTC QLQ-C30 v3 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Disease-related symptoms measured by EORTC QLQ-LC13 |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
| Measure: | Changes in WHO/ECOG performance status |
| Time Frame: | Up to 3 years after first patient randomized |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
- NSCLC
- PD-L1
- Durvalumab
- Tremelimumab
- PFS
- Overall survival (OS)
- Tumor Mutational Burden (TMB)
Last Updated
August 26, 2021
