A study to evaluate the benefit of adding durvalumab after chemotherapy, durvalumab and surgery in patients with early-stage, operable, non-small cell lung cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ETOP IBCSG Partners Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]

Trial duration

6 May 2025 → ongoing

Decision date (initial)

2024-09-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AG Switzerland

External identifiers

EU CT number

2023-508773-82-00

ClinicalTrials.gov

NCT06284317

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective of the study is to determine whether additional adjuvant immunotherapy after neoadjuvant chemo-immunotherapy has an effect on disease-free survival (DFS) in patients who do not achieve complete pathological response (PCR)as per local assessment according to the IASLC recommendations (Travis, Dacic et al. 2020).

Secondary objectives 2

1. To evaluate secondary measures of clinical efficacy in the adjuvant treatment phase, including DFS (in patients with pCR), overall survival, DFS according to ctDNA clearance, time to recurrence and overall safety.
2. Key secondary objective: The key secondary objective of the study is to explore the effect of additional adjuvant immunotherapy with durvalumab after neoadjuvant chemo-immunotherapy on DFS in all randomised patients, which is the Intention-To-Treat (ITT) cohort.

Conditions and MedDRA coding

Stage IIB-IIIB (N2) resectable non small cell lung cancer

Study design 7 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically confirmed NSCLC.
2. Stage IIB-IIIB (T1-4 N0-2) according to 8th edition of the TNM staging system of lung cancer. Stage III assessment should include samples of lymph nodes at levels 4, bilaterally, and level 7 to rule out stage IIIB N3 disease. T4 tumours will only be eligible if they are defined as T4 based only on their size (>7cm); any other reason will be considered ineligible.
3. Known PD-L1 status, as tested locally using a validated assay.
4. Absence of EGFR mutation or ALK translocation, as tested locally.
5. Adequate haematological, renal, and liver function.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
7. Age ≥18 at the time of enrolment.
8. Body weight >30 kg.
9. Life expectancy of at least 12 weeks.
10. Primary tumour resectable and functionally operable as assessed per local multidisciplinary tumour board (cardiac evaluation, pulmonary function and diffusion capacity, comorbidity).
11. Patient has to be fit to receive at least one of the protocol-defined platinum-based chemotherapy regimens, as per local standards.

Exclusion criteria 19

1. T4 with invasion of heart, great vessels, carina, trachea, oesophagus, or spine.
2. History of leptomeningeal carcinomatosis.
3. History of active primary immunodeficiency.
4. Active hepatitis infection.
5. Known HIV infection that is not well-controlled.
6. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
7. Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab.
8. Concurrent enrolment in another interventional clinical trial.
9. Known allergy or suspected hypersensitivity to durvalumab or its excipients.
10. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
11. Female patients who are pregnant or in the period of lactation.
12. Any previous or concurrent treatments for NSCLC.
13. Any previous immunotherapy.
14. Major surgical procedure (as per investigators assessment) within 28 days before enrolment.
15. History of allogenic organ transplantation.
16. Active or prior documented autoimmune disease or inflammatory disorders
17. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease (ILD) or serious chronic gastrointestinal conditions associated with diarrhoea.
18. Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
19. History of another primary malignancy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. DFS in patients without pCR, measured from randomisation.

Secondary endpoints 2

1. Assessed in the adjuvant treatment phase (after randomisation) • DFS in patients with pCR. • Overall survival (OS) in patients with/without pCR, ITT. • DFS in patients with/without ctDNA clearance. • Time to recurrence (TTR) in patients with/without pCR, ITT. • Time to treatment discontinuation (TTD) in patients with/without pCR, ITT. • Toxicity according to CTCAE v5.0.
2. Key secondary endpoint: (hierarchically tested) DFS in the ITT cohort (with and without pCR), measured from randomisation.

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ETOP IBCSG Partners Foundation

Sponsor organisation

ETOP IBCSG Partners Foundation

Address

Effingerstrasse 33

City

Bern

Postcode

3008

Country

Switzerland

Scientific contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Public contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Third parties 5

Locations

7 EU/EEA countries · 18 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

Documents 55 files

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

Application history

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