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 | 20.0 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
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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 |
Cohort 1: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1 positive patients [abbr. PD-L1+pts] (≥25% of tumour cells with membrane staining [abbr. Tcwmst]). Cohort 2: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1+pts (≥25% of Tcwmst). Cohort 3: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1+pts with ≥90% of Tcwmst. |
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E.2.2 | Secondary objectives of the trial |
Assess efficacy of MEDI4736 Cohort 1: 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 Tcwmst). Cohort 2, key sec objectives: in terms of ORR in Non-squamous [NSq] PD-L1+pts, PD-L1+pts with ≥90% of Tcwmst, NSq PD-L1+pts with ≥90% of Tcwmst. Other sec objectives: in terms of DoR, DCR, TTR, PFS and OS in PD-L1+pts, NSq PD-L1+pts, PD-L1+pts with ≥90% of Tcwmst, NSq PD-L1+pts with ≥90% of Tcwmst. Assess efficacy of MEDI4736 in PD-L1-pts (<25% of Tcwmst), NSq PD-L1-pts, PD-L1 unselected pts, PD-L1+pts with <90% of TCwmst, NSq PD-L1+pts with <90% of TCwmst. Cohorts 2 and 3: in a combined population of Cohorts 2 and 3 for: PD-L1+pts / NSq PD-L1+pts with ≥90% of Tcwmst. Cohort 3: in terms of DoR, DCR, TTR, PFS and OS in PD-L1+pts with ≥90% of Tcwmst. All cohorts: Assess safety, tolerability, PK and immunogenicity profile of MEDI4736 |
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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 |
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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 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 |
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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 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) (per RECIST 1.1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For each cohort, the data cut-off for the analysis of ORR will take place approximately 24 weeks after the last patient is enrolled into each cohort. |
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E.5.2 | Secondary end point(s) |
- Duration of response - Progression free survival - Disease control rate - Overall survival - Deep sustained response - AEs |
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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 approximately 12 months after the last patient is enrolled into each cohort. |
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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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 |
Philippines |
Singapore |
Taiwan |
Thailand |
United States |
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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
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The study will continue until the last patient completes 90 days of follow-up after MEDI4736 re-treatment or the last patient withdraws from the progression-free follow up (so no further patients are eligible for retreatment), whichever comes first.
In the event that a roll-over or safety extension study will become available, patients currently receiving treatment with study drug or patients in progression-free follow up may be transitioned to such a study, and the current study would end. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |