A Phase III Study of MEDI4736, given as Monotherapy or in Combination with Tremelimumab, versus Standard of Care in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer

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) - ARCTIC

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-000338-46-DE

Enrollment

1300

Registered

2014-07-24

Start date

2015-06-17

Completion date

Unknown

Last updated

2023-12-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) MedDRA version: 21.1 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864

Interventions

Trade Name: Gemcitabine 38mg/ml powder for solution for infusion Product Name: Gemcitabine Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: GEMCITABINE CAS Number: 95058-81-4

Eligibility

Sex/Gender

All

Inclusion criteria

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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1040 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 260

Exclusion criteria

Exclusion criteria: - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - 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 acute or chronic hepatitis B, C and HIV - Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy - Known EGFR TK activating mutations or ALK rearrangements. Patients with EGFR TK inactivating mutations eg, exon 20, are eligible. - 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)

Design outcomes

Primary

Measure	Time frame
Main Objective: Sub-study A (PD-L1-positive population): To assess the efficacy of MEDI4736 monotherapy compared with Standard of Care in terms of Overall survival (OS) and Progression free survival (PFS). Sub-study B (PD-L1-negative population): To assess the efficacy of MEDI4736 plus tremelimumab treatment compared with Standard of Care in terms of OS and PFS.;Secondary Objective: For both substudies A and B: - To assess the efficacy in terms of: Proportion of patients alive at 12 months from randomisation (OS12), Objective response rate (ORR), Duration of response (DoR), Proportion of patients alive and progression free at 6 months (APF6) and 12 months (APF12) from randomisation, and Time from randomisation to second progression (PFS2). - To assess the safety and tolerability profile - To assess the PK of MEDI4736 and tremelimumab - To investigate the immunogenicity of MEDI4736 and tremelimumab - To assess symptoms and health-related Quality of Life In addition for Sub-study B: - To evaluate the efficacy of MEDI4736+tremelimumab treatment compared with a) MEDI4736 monotherapy and b) tremelimunab monotherapy ;Primary end point(s): - Overall survival (OS) - Progression free survival (PFS);Timepoint(s) of evaluation of this end point: - OS: up to 3 years after first patient randomized - PFS: up to 3 years after first patient randomized	—

Measure

Time frame

Main Objective: Sub-study A (PD-L1-positive population): To assess the efficacy of MEDI4736 monotherapy compared with Standard of Care in terms of Overall survival (OS) and Progression free survival (PFS). Sub-study B (PD-L1-negative population): To assess the efficacy of MEDI4736 plus tremelimumab treatment compared with Standard of Care in terms of OS and PFS.;Secondary Objective: For both substudies A and B: - To assess the efficacy in terms of: Proportion of patients alive at 12 months from randomisation (OS12), Objective response rate (ORR), Duration of response (DoR), Proportion of patients alive and progression free at 6 months (APF6) and 12 months (APF12) from randomisation, and Time from randomisation to second progression (PFS2). - To assess the safety and tolerability profile - To assess the PK of MEDI4736 and tremelimumab - To investigate the immunogenicity of MEDI4736 and tremelimumab - To assess symptoms and health-related Quality of Life In addition for Sub-study B: - To evaluate the efficacy of MEDI4736+tremelimumab treatment compared with a) MEDI4736 monotherapy and b) tremelimunab monotherapy ;Primary end point(s): - Overall survival (OS) - Progression free survival (PFS);Timepoint(s) of evaluation of this end point: - OS: up to 3 years after first patient randomized - PFS: up to 3 years after first patient randomized

—

Secondary

Measure	Time frame
Secondary end point(s): - Proportion of patients alive at 12 months from randomisation (OS12) - Objective response rate (ORR) - Duration of response (DoR) ;Timepoint(s) of evaluation of this end point: - OS12: up to 1 year after last patient randomized - ORR: up to 3 years after the first patient randomized - DoR: up to 3 years after the first patient randomized	—

Countries

Argentina, Australia, Belgium, Canada, Chile, Czech Republic, European Union, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Philippines, Poland, Russian Federation, Serbia, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

Public ContactInformation Centre

AstraZeneca AB

information.centre@astrazeneca.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026