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: 21.1 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 100000004864; MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-07-21
• Last Update Posted: 11 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 1000

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. Provision of an archived tumour tissue block where such samples exist in a quantity sufficient to allow for analysis.
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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 530
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 470

Exclusion Criteria

- Either Previous drug assignment in the present study or Prior randomisation or treatment in a previous durvalumab (MEDI4736) and/or tremelimumab clinical study regardless of treatment arm assignment
- Participation in another clinical study with an investigational product during the last 4 weeks
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
- Mixed small cell and non-small cell lung cancer histology
- Receipt of sequential chemoradiation therapy for locally advanced NSCLC
- Patients with locally advanced NSCLC who have progressed whilst receiving definitive platinum based, concurrent chemoradiation therapy
- Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first dose of study drug
- 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 as prophylaxis against or to manage toxicities arising from chemotherapy and/or radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- Any unresolved toxicity CTCAE >Grade 2 from the prior
chemoradiation therapy.
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.
- Patients with = grade 2 pneumonitis from prior chemoradiation therapy
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- Recent major surgery within 4 weeks
- Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
- Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
- History of primary immunodeficiency
- History of organ transplant that requires therapeutic immunosuppression
- History of hypersensitivity to MEDI4736 or any excipient
- Uncontrolled intercurrent illness
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study drug.
- History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated in situ malignancies such as basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
- 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
- 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