A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer (ARCTIC)

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Non - Small Cell Lung Cancer NSCLC

Treatments: Drug: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4); Drug: Vinorelbine; Drug: tremelimumab (anti-CTLA4); Drug: Gemcitabine; Drug: MEDI4736 (durvalumab); Drug: Erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02352948

2014-000338-46 (EudraCT Number)

D4191C00004

Details and patient eligibility

About

This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in NSCLC patients with PD-L1 positive tumours and the combination of MEDI4736 (durvalumab) plus tremelimumab (MEDI4736+treme) versus Standard of Care in NSCLC patients with PD-L1-negative tumours in the treatment of male and female patients with locally advanced or metastatic NSCLC (Stage IIIB-IV), who have received at least 2 prior systemic treatment regimens including 1 platinum-based chemotherapy regimen for NSCLC. Patients with known EGFR (Epidermal growth factor receptor) tyrosine kinase (TK) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements are not eligible for the study (prospective testing is not planned within this study). The Standard of Care options are: an EGFR tyrosine kinase inhibitor (erlotinib [TARCEVA®]), gemcitabine or vinorelbine (NAVELBINE®)

Full description

The study has an umbrella design with 2 sub-studies: sub-study A (randomizing patients with PD-L1 positive tumours 1:1 into MEDI4736 (durvalumab) vs. Standard of Care) and sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736 (durvalumab) vs. MEDI4736 (durvalumab) plus tremelimumab vs. tremelimumab vs. Standard of Care. The two substudies may have different durations of recruitment periods due to differences in patient population (PD-L1 expression). They may not run concurrently with start and completion of recruitment potentially occurring at different time points.

Enrollment: 597 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged at least 18 years
• Documented evidence of NSCLC (Stage IIIB/ IV disease)
• Disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional regimen for treatment of NSCLC
• World Health Organization (WHO) Performance Status of 0 or 1
• Estimated life expectancy more than 12 weeks

Exclusion criteria

• Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti-CTLA4
• Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
• Active or prior documented autoimmune disease within the past 2 years
• Evidence of severe or uncontrolled systemic disease, including active bleeding diatheses or active infections including hepatitis B, C and HIV
• Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) >Grade 2 from previous anti-cancer therapy
• Known EGFR TK activating mutations or ALK rearrangements
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
• Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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597 participants in 6 patient groups

MEDI4736 (durvalumab) monotherapy in Sub-study A

Experimental group

Description:

MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.

Treatment:

Drug: MEDI4736 (durvalumab)

Standard of Care in Sub-study A

Active Comparator group

Description:

Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.

Treatment:

Drug: Erlotinib

Drug: Gemcitabine

Drug: Vinorelbine

MEDI4736 (durvalumab) + tremelimumab in Sub-study B

Experimental group

Description:

MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Treatment:

Drug: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)

Standard of Care in Sub-study B

Active Comparator group

Description:

Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.

Treatment:

Drug: Erlotinib

Drug: Gemcitabine

Drug: Vinorelbine

MEDI4736 (durvalumab) monotherapy in Sub-study B

Experimental group

Description:

MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Treatment:

Drug: MEDI4736 (durvalumab)

tremelimumab in Sub-study B

Experimental group

Description:

tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Treatment:

Drug: tremelimumab (anti-CTLA4)