A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 in Completely Resected Non-Small Cell Lung Cancer (BR31)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NVALT-studies Stichting, Intergroupe Francophone De Cancerologie Thoracique, Fundacion GECP, Queen's University, Clinipace Global Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Mar 2015 → 12 Apr 2025

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517856-36-00

EudraCT number

2014-004946-83

ClinicalTrials.gov

NCT02273375

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy, Therapy

To assess in comparison to placebo, the impact of adjuvant therapy with MEDI4736 given by
intravenous infusion for one year on the disease free survival of patients with completely resected
(stage IB ≥ 4cm, stage II or IIIA), non-small cell lung cancer that is PD-L1 expression TC ≥ 25%,
and EGFR-/ALK-.

Secondary objectives 10

1. To compare the disease free survival in the MEDI4736 arm to the placebo arm in the remaining 5 patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
2. To compare the overall survival in the MEDI4736 arm to the placebo arm in the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
3. To compare lung cancer specific survival in the MEDI4736 arm to the placebo arm in the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
4. To evaluate the nature, severity, and frequency of toxicities, between arms.
5. To evaluate the quality of life between the two arms in the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
6. To determine the survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile, and the factors influencing their preferences.
7. To determine the incremental cost effectiveness and cost utility ratios for MEDI4736.
8. To evaluate the prognostic and predictive significance of PD-L1 expression.
9. To evaluate changes in plasma/serum cytokines and other blood and tissue based biomarkers after treatment with MEDI4736 and at the first disease event (relapse or new invasive primary malignancy).
10. To explore polymorphisms that may be associated with outcomes.

Conditions and MedDRA coding

Completely resected primary stage IB (≥ 4cm), II and IIIA non-small cell lung cancer patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung according to WHO Classification of Tumours (WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. WHO/IARC Classification of Tumours, 4th Edition, Volume 7). Patients with large-cell neuroendocrine carcinomas are not eligible.
2. Patients must be classified post-operatively as Stage IB (≥ 4cm in the longest diameter), II or IIIA on the basis of pathologic criteria.
3. Surgery: -A pre-surgical PET scan of the thorax and a MRI or CT scan of the brain is considered standard of care and thus must be done prior to surgery. Patients in whom this was not done prior to surgery may still be enrolled providing that appropriate imaging is performed prior to randomization. -Complete surgical resection of the primary NSCLC is also mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. Resection may be accomplished by open or VATS techniques. -Lymph node mapping is defined by The International Association for the Study of Lung Cancer (IASLC) lymph node map. The nodal tissue should be labelled according to the recommendations of the American Thoracic Society. Surgeons are strongly encouraged to dissect or sample all accessible nodal levels in accordance with the European Society of Thoracic Surgeons guidelines. Accordingly, it is recommended that a minimum of 3 (three) lobe specific mediastinal nodal stations (N2), one of which should include station 7, and at least one N1 station - inclusive of the ones removed with the pulmonary specimen have been sampled at the end of the procedure. -If preoperative CT and/or PET are suspicious for mediastinal nodal involvement, it is recommended that invasive mediastinal staging with mediastinoscopy or EBUS-TBNA be performed. Station 5 or 6 lymph nodes may be accessed by anterior mediastinotomy or VATS. This may also occur at the time of the surgical resection. If invasive staging shows disease in regional lymph nodes, they must be surgically removed. It is recommended that complete mediastinal lymph node dissection be undertaken for stage IIIA tumours. -Surgery may consist of lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the intraoperative findings. Patients who have had only segmentectomies or wedge resections are not eligible for this study. Note: Where a resection has been extended by means of a wedge resection of an adjacent lobe in order to ensure complete resection of a tumour at or crossing a fissure between lobes, as long as the margins are clear this is acceptable. Where the resection of a second tumour nodule, even where not considered to be a co-primary, is undertaken by means of a wedge resection of a separate lobe then the patient is not eligible.

Exclusion criteria 3

1. A combination of small cell and non-small cell lung cancer, pulmonary carcinoid tumour or large-cell neuroendocrine carcinoma (LCNEC).
2. Patients with a history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other malignancies curatively treated with no evidence of disease for ≥ 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
3. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: patients with Grave’s disease and/or psoriasis not requiring systemic therapy within the last two years from randomization and patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement are not excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival (DFS) for patients with NSCLC that is PD-L1 expression TC ≥ 25% and EGFR-/ALK-.

Secondary endpoints 10

1. DFS in the remaining 5 patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
2. Overall survival (OS) for patients in the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
3. Lung cancer specific survival for patients in the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
4. Adverse effects and tolerability of MEDI4736.
5. Quality of life in the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status.
6. Survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile.
7. Economic evaluation (cost effectiveness and cost utility).
8. Evaluation of predictive/prognostic significance of PD-L1 expression.
9. Evaluation of changes in plasma/serum cytokines and other blood and tissue based biomarkers after treatment with MEDI4736 and at disease event.
10. Exploratory pharmacogenomic assays (baseline only).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NVALT-studies Stichting

Sponsor organisation

NVALT-studies Stichting

Address

Mercatorlaan 1200

City

Utrecht

Postcode

3528 BL

Country

Netherlands

Scientific contact point

Organisation

NVALT-studies Stichting

Contact name

Lizza Hendriks

Public contact point

Organisation

NVALT-studies Stichting

Contact name

Lizza Hendriks

Intergroupe Francophone De Cancerologie Thoracique

Sponsor organisation

Intergroupe Francophone De Cancerologie Thoracique

Address

10 Rue De La Grange Bateliere

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Operations Cliniques

Public contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Operations Cliniques

Fundacion GECP

Sponsor organisation

Fundacion GECP

Address

Avinguda Meridiana 358 6 Planta

City

Barcelona

Postcode

08027

Country

Spain

Queen's University

Sponsor organisation

Queen's University

Address

99 University Avenue

City

Kingston

Postcode

K7L 3N5

Country

Canada

Scientific contact point

Organisation

Queen's University

Contact name

Dr. Chris O'Callaghan

Public contact point

Organisation

Queen's University

Contact name

CCTG Regulatory Affairs

Clinipace Global Limited

Sponsor organisation

Clinipace Global Limited

Address

Beechwood Grove Business Park, Oakwood, Grove Park Industrial Estate, Waltham Road Oakwood Grove Park Industrial Estate

City

Maidenhead

Postcode

SL6 3LW

Country

United Kingdom

Sponsor responsibilities

Contact point sponsor

NVALT-studies Stichting

Article 77 implementation

NVALT-studies Stichting

Locations

8 EU/EEA countries · 103 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications