Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) MedDRA version: 18.0 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 100000004864 MedDRA version: 18.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: MEDI4736
Current Sponsor code: MEDI4736
Other descriptive name: MEDI4736
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed, written and dated informed consent prior to any study specific procedures 2. Male or female aged 18 years or older 3. Patients must have EITHER • Histologically- or cytologically-documented NSCLC), OR • Recurrent or progressive disease following multimodal therapy for locally advanced disease) 4. Patients must have received at least 2 prior systemic treatment regimens for treatment of NSCLC 5. Patients must have experienced disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional systemic therapy 6. Patient's tumour sample must be PD-L1 positive 7. Patients must have measurable disease 8. Life expectancy =12 weeks at Day 1 9. World Health Organisation (WHO) Performance Status of 0 or 1 10. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients 11. Adequate organ and marrow function 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 594 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 806
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical study with an investigational product (IMP) during the last 4 weeks 2. Concurrent enrolment 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 and NSCLC histology 4. Receipt of any immunotherapy, or IMP within 4 weeks prior to the first dose of study drug 5. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody 6. Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy 7. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 8. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment 9. Receipt of radiation therapy within 4 weeks prior to starting MEDI4736, or limited field of radiation for palliation within 2 weeks of the first dose of MEDI4736 10. Recent major surgery within 4 weeks 11. Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment 12. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) 13. History of primary immunodeficiency 14. History of allogeneic organ transplant 15. History of hypersensitivity to MEDI4736 or any excipient 16. Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study 17. Uncontrolled intercurrent illness 18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736 19. 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 study drug 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. 20. Female patients who are pregnant or breast-feeding. Male or female patients of reproductive potential who are not using an effective method of birth control 21. Any condition that, in the opinion of the investigator, would interfere with evaluation of MEDI4736 or interpretation of patient safety or study results 22. Absence of a tumour sample (archival and recent).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort 1: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1 positive patients (=25% of tumour cells with membrane staining) (abbr. as PD-L1+pts). Cohort 2: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1+pts (=25% of tumour cells with membrane staining). Cohort 3: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1+pts with =90% of tumour cells with membrane staining.;Secondary Objective: Cohort 1: To further assess the efficacy of MEDI4736 in terms of Duration of response (DoR), Disease control rate (DCR), Time to response (TTR), Progression free survival (PFS), and Overall survival (OS) in PD-L1+pts (=25% of tumour cells with membrane staining). Cohort 2: Key secondary objectives: To assess the efficacy of MEDI4736 in terms of ORR in Non-squamous PD-L1+pts and Non-squamous PD-L1 unselected pts. Other secondary objectives: To further assess the efficacy of MEDI4736 in terms of DoR, DCR, TTR, PFS and OS in PDL1+ pts, Non-squamous PD-L1+pts, and Non-squamous PD-L1 unselected pts. To assess the efficacy of MEDI4736 in PD-L1-pts (<25% of tumour cells with membrane staining), Non-squamous PD-L1-pts, and PD-L1 unselected pts. Cohort 3: To further assess the efficacy of MEDI4736 in terms of: DoR,DCR, TTR, PFS and OS in PD-L1+pts with =90% of tumour cells with membrane staining. All cohorts: To assess the safety, tolerability, PK and immunogenicity profile of MEDI4736;Primary end point(s): Objective response rate (ORR) (per RECIST 1.1);Timepoint(s) of evaluation of this end point: The data cut-off for analysis of ORR will take place approximately 8 months after recruitment ends. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Duration of response - Progression free survival - Disease control rate - Overall survival - Deep sustained response - AEs;Timepoint(s) of evaluation of this end point: The data cut-off for analysis of the secondary efficacy endpoints will take place approximately 8 months after recruitment ends. The final analysis of OS (secondary endpoint) will take place 12 months after recruitment ends. | — |
Countries
Austria, Belgium, Canada, Czech Republic, European Union, Germany, Hungary, Italy, Japan, Korea, Republic of, Philippines, Poland, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed