E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) |
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E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029514 |
E.1.2 | Term | Non-small cell lung cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess the efficacy of MEDI4736 treatment in terms of objective response rate (ORR) |
|
E.2.2 | Secondary objectives of the trial |
- To further assess the efficacy of MEDI4736 in terms of: Duration of response (DoR), Progression free survival (PFS), Disease control rate (DCR), Overall survival (OS), and Deep sustained response (DSR)
- To assess the safety, tolerability, PK and immunogenicity profile of MEDI4736 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Research |
|
E.3 | Principal 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 |
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E.4 | Principal 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 organ transplant that requires therapeutic
Immunosuppression
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 within 5 years prior to starting MEDI4736, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
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) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) (per RECIST 1.1) |
|
E.5.1.1 | 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. |
|
E.5.2 | Secondary end point(s) |
- Duration of response
- Progression free survival
- Disease control rate
- Overall survival
- Deep sustained response
- AEs |
|
E.5.2.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
European Union |
Japan |
Korea, Republic of |
Malaysia |
Philippines |
Singapore |
Taiwan |
Thailand |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is defined as ‘the last visit of the last patient undergoing the study’. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |