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.

NCT06284317 | Recruiting Phase 3 DMC

• 1 other identifier: ETOP 25-23
• Study Type: interventional
• Target: 290
• Locations: 9 countries
• Sites: 41

Brief Summary

ADOPT-lung is an international, multicentre, open-label randomised phase III trial. Protocol treatment consists of 3-4 cycles of neoadjuvant durvalumab in combination with platinum-based doublet chemotherapy, followed by surgery. Patients with R0 and R1 only resection will be randomised to receive either adjuvant durvalumab for 12 cycles (experimental arm) or observation (control arm). The primary objective of the study is to determine whether additional adjuvant immunotherapy with durvalumab 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.

Conditions

Non Small Cell Lung Cancer

Keywords

IIB-IIIB (N2) resectable NSCLC; Durvalumab

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS)

  Assessed in the adjuvant treatment phase. DFS is defined as the time from the date of randomisation until disease recurrence (including loco-regional recurrence, a distant (metastatic) recurrence or a second primary) or death from any cause. Censoring (for patients without recurrence/death) will occur at the date of last tumour assessment. Patients without a post-randomisation tumour assessment will be censored at the date of randomisation (plus 1 day). DFS will be assessed in patients without pCR (primary endpoint), as well as in patients with pCR (secondary endpoint) and in patients with/without ctDNA clearance (secondary endpoints).

  From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

Secondary Outcomes (6)

• DFS in patients with pCR

  From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

• Overall survival (OS) in patients with/without pCR

  From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

• DFS in patients with/without ctDNA clearance

  From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

• Time to recurrence (TTR) in patients with/without pCR

  From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

• Time to treatment discontinuation (TTD) in patients with/without pCR

  From the date of randomisation until last patient last visit (approximately 60 months after randomisation of the first patient)

Other Outcomes (7)

• Correlation between ctDNA clearance and DFS

  From the date of screening until last patient last visit (approximately 60 months after randomisation of the first patient)

• Correlation between ctDNA clearance and OS

  From the date of screening until last patient last visit (approximately 60 months after randomisation of the first patient)

• Correlation between ctDNA clearance and initial PD-L1 assessment

  From the date of screening until last patient last visit (approximately 60 months after randomisation of the first patient)

Study Arms (2)

Durvalumab

EXPERIMENTAL

Protocol treatment in the adjuvant phase consists of adjuvant durvalumab

Drug: Adjuvant durvalumab

Observation

NO INTERVENTION

Observation only

Interventions

Adjuvant durvalumab DRUG

Durvalumab is given at a fixed dose of 1500 mg i.v. every 4 weeks (±1 week) until relapse or unacceptable toxicity, for a maximum of 12 cycles after surgery.

Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed NSCLC.
• 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.
• Known PD-L1 status, as tested locally using a validated assay. To ensure comparability of results, it is strongly encouraged that PD-L1 testing is done with the Ventana PD-L1 (SP263) assay.
• Absence of EGFR mutation or ALK translocation, as tested locally.
• Primary tumour resectable and functionally operable as assessed per local multidisciplinary tumour board (cardiac evaluation, pulmonary function and diffusion capacity, comorbidity).
• Adequate haematological function:
• Haemoglobin ≥90 g/L, Absolute neutrophil count (ANC) ≥1.0× 109/L, Platelet count ≥75× 109/L.
• \- Adequate renal function: Measured creatinine clearance (CL) \>40 mL/min or calculated CL \>40 mL/min calculated by the Cockcroft-Gault.
• \- Adequate liver function: ALT and AST ≤2.5× institutional ULN, Total serum bilirubin ≤1.5× institutional ULN (patients with Gilbert's syndrome may be allowed to be enrolled after consultation with the Medical Affairs Team at the ETOP IBCSG Partners Foundation.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Age ≥18 at the time of enrolment.
• Body weight \>30 kg.
• Life expectancy of at least 12 weeks.

You may not qualify if:

• T4 with invasion of heart, great vessels, carina, trachea, oesophagus, or spine.
• Any previous or concurrent treatments for NSCLC.
• Any previous immunotherapy.
• Major surgical procedure (as per investigators assessment) within 28 days before enrolment.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune disease or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia. Patients with type I diabetes. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy. Patients without active disease in the last 5 years may be included but only after consultation with the Medical Affairs Team at the ETOP IBCSG Partners Foundation.
• Patients with celiac disease controlled by diet alone.
• 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.
• 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.
• 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 durvalumab 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• AstraZeneca: collaborator

Study Sites (42)

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

NOT YET RECRUITING

Nepean Hospital

Penrith, New South Wales, Australia

RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

NOT YET RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, Australia

NOT YET RECRUITING

Royal Hobart Hospital

Hobart, Tasmania, Australia

NOT YET RECRUITING

Eastern Health

Box Hill, Victoria, Australia

RECRUITING

Alfred Hospital

Melbourne, Victoria, Australia

RECRUITING

Peter MacCallum Cancer Centre

Parkville, Victoria, Australia

RECRUITING

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

NOT YET RECRUITING

Wien AKH

Vienna, Austria

RECRUITING

Institut Jules Bordet - HUB

Anderlecht, Belgium

RECRUITING

Antwerp University Hospital

Antwerp, Belgium

RECRUITING

North Estonia Medical Centre Foundation

Talinn, Estonia

RECRUITING

CHU Angers

Angers, France

RECRUITING

Institut Bergonié

Bordeaux, France

NOT YET RECRUITING

Le Mans - CHG

Le Mans, France

RECRUITING

Lyon - Centre Léon Bérard

Lyon, France

RECRUITING

Beaumont Hospital

Dublin, Ireland

RECRUITING

St James's Hospital

Dublin, Ireland

RECRUITING

SS Antonio e Biagio e Cesare Arrigo Hospital

Alessandria, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, Italy

RECRUITING

Perugia Hospital

Perugia, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori "Regina Elena"

Rome, Italy

RECRUITING

AOUS Policlinico Le Scotte

Siena, Italy

NOT YET RECRUITING

Universita di Verona - Department of Medicine

Verona, Italy

RECRUITING

NKI

Amsterdam, Netherlands

RECRUITING

UMCU

Utrecht, Netherlands

RECRUITING

Kantonsspital Baden

Baden, Switzerland

NOT YET RECRUITING

Universitätsspital Basel

Basel, Switzerland

RECRUITING

Eoc - Iosi

Bellinzona, Switzerland

NOT YET RECRUITING

Inselspital Bern

Bern, Switzerland

RECRUITING

HFR Hôpital Fribourgeois

Fribourg, Switzerland

RECRUITING

CHUV

Lausanne, Switzerland

NOT YET RECRUITING

Kantonsspital St.Gallen

Sankt Gallen, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, Switzerland

RECRUITING

University Hospital Zurich

Zurich, Switzerland

NOT YET RECRUITING

Barts Health NHS Trust

London, United Kingdom

RECRUITING

Royal Marsden Hospital (Chelsea)

London, United Kingdom

NOT YET RECRUITING

Royal Marsden Hospital (Sutton)

London, United Kingdom

NOT YET RECRUITING

Maidstone and Tunbridge Wells NHS Trust

Maidstone, United Kingdom

RECRUITING

Wythenshawe Hospital, Manchester University NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Solange Peters, MD-PhD

  Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

  STUDY CHAIR

• Sabine Schmid, MD

  Inselspital, Universitätsspital Bern, 3010 Bern, Switzerland

  STUDY CHAIR

• Paul Van Schil, MD-PhD

  Antwerp University Hospital, Antwerp, Belgium,

  STUDY CHAIR

• Stephen Finn, MD-PhD

  St. James's Hospital, Dublin 8, Ireland

  STUDY CHAIR

Central Study Contacts

Heidi Roschitzki, PhD

CONTACT

+41 31 511 94 00; heidi.roschitzki@etop.ibcsg.org

Susanne Roux

CONTACT

+41 31 511 94 00; ADOPT-lung@etop.ibcsg.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: February 28, 2024
• Study Start: January 15, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

NL (2); BE (2); CH (9); AU (10); ES (1); IT (6); FR (4); IE (2); GB (5)