Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer (nsclc)
Treatments medi4736, vinorelbine, gemcitabine, erlotinib, medi4736 in combination with tremelimumab (anti-ctla4), tremelimumab (anti-ctla4)
Phase phase 3
Targets EGFR, CTLA-4, PD-1
Sponsor AstraZeneca
Start date January 2015
End date March 2017
Trial size 730 participants
Trial identifier NCT02352948, D4191C00004

Summary

This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 versus Standard of Care in NSCLC patients with PD-L1 positive tumours and the combination of MEDI4736 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®).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
MEDI4736 by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.
medi4736
MEDI4736 treatment by intravenous infusion
(Active Comparator)
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
vinorelbine
Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.
gemcitabine
Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.
erlotinib
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
(Experimental)
MEDI4736 by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
medi4736 in combination with tremelimumab (anti-ctla4)
MEDI4736 in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion
(Active Comparator)
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
vinorelbine
Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.
gemcitabine
Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.
erlotinib
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
(Experimental)
MEDI4736 by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
medi4736
MEDI4736 treatment by intravenous infusion
(Experimental)
tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
tremelimumab (anti-ctla4)
tremelimumab (anti-CTLA4) treatment by intravenous infusion

Primary Outcomes

Measure
Overall Survival (OS)
time frame: up to 3 years after first patient randomized
Progression Free Survival (PFS)
time frame: up to 3 years after the first patient randomized

Secondary Outcomes

Measure
Proportion of patients alive at 12 months from randomization (OS12)
time frame: up to 1 year after last patient randomized
Objective Response Rate (ORR)
time frame: up to 3 years after the first patient randomized
Duration of Response (DoR)
time frame: up to 3 years after the first patient randomized

Eligibility Criteria

Male or female participants from 18 years up to 130 years old.

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)

Additional Information

Official title A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, 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 (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).
Description The study has an umbrella design with 2 sub-studies in: sub-study A (randomizing patients with PD-L1 positive tumours 1:1 into MEDI4736 vs. Standard of Care) and sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736 vs. MEDI4736 plus tremelimumab vs. tremelimumab vs. Standard of Care. Two substudies may have different duration of recruitment period due difference in patients population (PD-L1 expression). They may not run concurrently with start and completion of recruitment potentially occuring at different time points.
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.