A Phase II Study of MEDI4736 in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 1

Conditions: ocally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV)
MedDRA version: 19.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864
MedDRA version: 19.0Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-005427-16-PL

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1400

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 with =25% of tumour cells with membrane staining (Cohorts 1 and 2) or PD-L1 positive with =90% of tumour cells with membrane staining (Cohort 3).
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

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).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method