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

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Non Small Cell Lung Cancer NSCLC

Treatments: Drug: Pemetrexed + cisplatin; Drug: Gemcitabine + carboplatin; Drug: Tremelimumab; Drug: Durvalumab; Drug: Gemcitabine + cisplatin; Drug: Pemetrexed + carboplatin; Drug: Abraxane + carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03164616

2017-000920-81 (EudraCT Number)

D419MC00004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,186 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,186 participants in 3 patient groups

Treatment Arm 1

Experimental group

Description:

durvalumab + tremelimumab combination therapy + SoC chemotherapy

Treatment:

Drug: Pemetrexed + carboplatin

Drug: Abraxane + carboplatin

Drug: Gemcitabine + cisplatin

Drug: Durvalumab

Drug: Tremelimumab

Drug: Gemcitabine + carboplatin

Drug: Pemetrexed + cisplatin

Treatment Arm 2

Experimental group

Description:

durvalumab monotherapy + SoC chemotherapy

Treatment:

Drug: Pemetrexed + carboplatin

Drug: Abraxane + carboplatin

Drug: Gemcitabine + cisplatin

Drug: Durvalumab

Drug: Gemcitabine + carboplatin

Drug: Pemetrexed + cisplatin

Treatment Arm 3

Active Comparator group

Description:

SoC chemotherapy alone

Treatment:

Drug: Pemetrexed + carboplatin

Drug: Abraxane + carboplatin

Drug: Gemcitabine + cisplatin

Drug: Gemcitabine + carboplatin

Drug: Pemetrexed + cisplatin