A Phase III Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

Phase 1

• Conditions: ocally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III); MedDRA version: 17.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864; MedDRA version: 17.0Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000336-42-IT
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-07-04
• Last Update Posted: 12 March 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 880

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 histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease
4. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.
5. Patients must have not progressed following definitive, platinumbased, concurrent chemoradiation therapy.
6. Patients must provide an archival tumour sample.
7. Life expectancy =12 weeks
8. World Health Organization (WHO) Performance Status of 0 or 1
9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
10. 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 484
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 396

Exclusion Criteria

1. Participation in another clinical study with an investigational product 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 non-small cell lung cancer histology
4. Receipt of sequential chemoradiation therapy for locally advanced NSCLC
5. Patients with locally advanced NSCLC who have progressed whilst receiving definitive platinum based, concurrent chemoradiation therapy
6. Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first dose of study drug
7. Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to
manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
8. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
9. Any unresolved toxicity CTCAE >Grade 2 from the prior
chemoradiation therapy.
10. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (eg, hearing loss) after consultation with the AstraZeneca/MedImmune medical monitor.
11. Patients with any grade pneumonitis from prior chemoradiation therapy
12. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
13. Recent major surgery within 4 weeks
14. Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
15. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
16. History of primary immunodeficiency
17. History of organ transplant that requires therapeutic
immunosuppression
18. History of hypersensitivity to MEDI4736 or any excipient
19. Uncontrolled intercurrent illness
20. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study drug.
21. History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
22. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
23. Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of MEDI4736 treatment compared with placebo in terms of OS and PFS;Secondary Objective: - To further assess the efficacy of MEDI4736 compared with placebo in terms of: OS24, ORR, DoR, APF12, APF18, PFS2 and DSR<br>- To assess the safety and tolerability profile of MEDI4736 compared with placebo<br>- To assess symptoms and health-related quality of life in patients treated with MEDI4736 compared with placebo;Primary end point(s): Both Progression free survival (PFS) and Overall survival (OS) are co-primary endpoints.;Timepoint(s) of evaluation of this end point: OS - Overall Survival is defined as the time from the date of randomization until death due to any cause. Estimated to be from baseline up to 5 years.<br>PFS - Progression-Free Survival is defined as the time from randomization until the date of objective disease progression or death. Estimated to be from baseline up to 5 years.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Proportion of patients alive at 24 months from randomization (OS24)<br>- Objective response rate (ORR) ;Timepoint(s) of evaluation of this end point: - OS24: The proportion of patients alive at 24 months. Estimated to be from baseline up to 5 years.<br>- ORR: Defined as the number (%) of patients with at least 1 visit response of CR (Complete response) or PR (Partial response) and will be based on all randomised patients who have measurable disease. Study data collection expected to last for approximately 3 years.