Health Condition 1: null- Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC)
Conditions
Interventions
Intervention1: MEDI4736 along with Standard of Care therapy: Along with Standard of Care therapy
Control Intervention1: Standard of Care therapy: Standard of Care therapy
Sponsors
AstraZeneca AB
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age greater than or equal to 18 years at the time of screening 2. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 3. Histologically or cytologically documented Stage IV NSCLC not amendable to curative surgery or radiation (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology; IASLC Staging Manual in Thoracic Oncology). 4. Patients must have tumors that lack activating EGFR mutation (eg, exon 19 deletion or exon 21 L858R, exon 21 L861, exon 18 G719, or exon 20 S7681 mutation) and ALK rearrangement. (If a patient has squamous histology or is known to have a tumor with a KRAS mutation, then EGFR and ALK testing is not required). 5. No prior chemotherapy or any other systemic therapy for advanced or metastatic NSCLC. Patients who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred >6 months from last therapy. 6. Tumor PD-L1 status, confirmed by a reference laboratory using the Ventana IHC assay, must be known prior to randomization. As such, all patients must be able to undergo a fresh tumor biopsy during screening or to provide an available tumor sample taken 7. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment. 8. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as >=10 mm in the longest diameter (except lymph nodes which must have a short axis >=15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. 9. No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines. 10. Adequate organ and marrow function as defined below: - Hemoglobin >=9.0 g/dL - Absolute neutrophil count >=1.5 Ã? 109 /L - Platelet count >=100 Ã? 109/L - Serum bilirubin - ALT and AST - Calculated creatinine clearance (CL) >50 mL/min as determined
Exclusion criteria
Exclusion criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 2. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study 3. Mixed small-cell lung cancer and NSCLC histology or not otherwise specified (NSCLC NOS). 4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. 5. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable. 6. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 7. History of allogenic organ transplantation 8. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohnâ??s disease], diverticulitis with the exception of diverticulosis, celiac disease or other serious GI chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Gravesâ?? disease, rheumatoid arthritis, hypophysitis, uveitis, etc within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment 9. Any condition that, in the opinion of the Investigator, would interfere with the evaluation of IP or interpretation of patient safety or study results, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from MEDI4736 or tremelimumab, or compromise the ability of the patient to give written informed consent. 10. Medical contraindication to platinum (cisplatin or carboplatin)-based doublet chemotherapy. 11. History of another primary malignancy except for - Malignancy treated with curative intent and with no known active disease >=5 years before the first dose of IP and of low potential risk for recurrence - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ) 12. History of leptomeningeal carcinomatosis 13. Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment. Patients with suspected brain meta
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to Standard of Care (SoC) in terms of OS in patients with Non Small Cell Lung Cancer (NSCLC) Timepoint: Overall Survival (OS) (Time frame-Approximately 4 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the efficacy of MEDI4736 plus tremelimumab combination therapy compared to SoC in terms of Overall Survival in patients with PD-L1â?? negative NSCLC Timepoint: OS in patients with PD-L1â??negative NSCLC (Time frame-Approximately 4 years);To assess the Pharmacokinetics (PK) of MEDI4736 plus tremelimumab combination therapy Timepoint: Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK parameters, such as peak concentration and trough (as data allow; sparse sampling) (Time frame-Approximately 4 years) ;To further assess the efficacy of MEDI4736 plus tremelimumab combination therapy compared to SoC in terms of - Progression-free survival (PFS) - Objective response rate (ORR) - Duration of response (DoR) - Proportion of patients alive at 18 months (OS18) - Proportion of patients alive and progression free at 12 months (APF12) - Progression-free survival after subsequent anticancer therapy (PFS2)Timepoint: - PFS, and ORR in patients with PD-L1â??negative NSCLC - PFS, ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1 PFS2 using local standard clinical practice OS12 and OS18 (Time frame-Approximately 4 years);To investigate the immunogenicity of MEDI4736 and tremelimumab Timepoint: Presence of ADAs for MEDI4736 and tremelimumab (confirmatory results: positive and negative; titers) (Time frame-Approximately 4 years) | — |
Countries
Argentina, Brazil, Bulgaria, Chile, Denmark, Finland, Greece, Hong Kong, India, Israel, Japan, Malaysia, Mexico, Peru, Philippines, Poland, Portugal, Qatar, Republic of Korea, Romania, Saudi Arabia, Singapore, Sweden, Turkey, Ukraine, United Arab Emirates, United Kingdom, United States of America
Contacts
Public ContactTapankumar M Shah
AstraZeneca Pharma India Limited
Outcome results
None listed