Durvalumab(MEDI4736) After chemoRadioTherapy(DART) for NSCLC-a Translational and Biomarker Study

NCT04392505 | Active Not Recruiting Phase 2

• 1 other identifier: DART
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 10

Brief Summary

The main aim is to identify and describe biomarkers in different sample types related to chemoradiation followed by durvalumab treatment for stage III PD-L1 negative and positive non-small cell lung cancer (NSCLC) patients' eligible for curatively intended chemoradiation. The hypothesis is that clinical differences in course of disease reflect underlying biological characteristics.

Conditions

Cancer; Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Stage III; NSCLC; NSCLC, Stage III

Outcome Measures

Primary Outcomes (1)

• Impact of tumour mutational burden (TMB) measured in the tumour tissue and blood samples, on the hazard.

  Analyses of TMB in tumour tissue. Patients with high Tumour Mutational Burden, TMB (\> 8.5 mutations per megabase) have a hazard ratio equal to or less than 0.55 as compared to patients with low TMB. Tumor tissue will be analysed in regard to TMB, and several different cut-offs will be evaluated.

  Throughout study, up to 5 years

Secondary Outcomes (7)

• Predict assosiation between Tumour Mutational Burden, TMB, measured in tumour tissue and blood samples and clinical response

  Through study, up to 5 years

• Specific RNA profiles predict response to treatment

  Through study, up to 5 years

• Impact of Molecular profiles in urine on response to treatment

  Through study, up to 5 years

• Analysis of pre-treatment and under-treatment samples may identify biomarkers for predicting which patients will benefit from treatment with durvalumab after chemoradiation

  Through study, up to 5 years

• The durvalumab treatment following chemoradiation will induce T cell responses against antigens expressed in each patient´s tumor.

  Through study, up to 5 years

Other Outcomes (1)

• The gut microbiome influence the responses to chemoradiation followed by durvalumab

  Through study, up to 5 years

Study Arms (1)

The whole study population

EXPERIMENTAL

All patients will receive durvalumab for up to 1 months after standard treatment With chemoradiotherapy.

Drug: Durvalumab Injection

Interventions

Durvalumab Injection DRUG

Included patients will receive durvalumab (fixed dose, 1500mg Q4W) until progressive disease and no clinical benefit, intolerable toxicity or patient's wish, for a maximum duration of 12 months. Treatment with durvalumab should start \<5 weeks after last radiotherapy dosing.

Also known as: Imfinzi

The whole study population

Eligibility Criteria

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

You may qualify if:

• Locally-advanced, unresectable, stage III NSCLC (including PET-CT and MRI-brain in the diagnostic work-up).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Diagnostic biopsy with PD-L1 \<1% in 50 patients PD-L1 ≥1% in 50 patients
• Adequate core or excisional biopsy for tumor assessment
• Age \> 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least 12 weeks
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• \- Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3)
• Platelet count ≥100 x 109/L (\>75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

You may not qualify if:

• Non-small cell lung cancer disease suitable for curative surgery
• Significant cardiac, pulmonary or other medical illness that would limit activity or survival
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study during the last 2 weeks.
• Any concurrent chemotherapy, Investigational Product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], 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 hypothyroidism (e.g., following Hashimoto syndrome) stableon 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 study physician
• Patients with celiac disease controlled by diet alone
• i. 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, serious chronic gastrointestinal conditions associated with diarrhea, or 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 j. 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 IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

Sponsors & Collaborators

• Oslo University Hospital: lead
• AstraZeneca: collaborator

Study Sites (10)

North Estonia Medical Centre

Tallinn, Estonia

Location

Oulu University Hospital

Oulu, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Turku University Hospital

Turku, Finland

Location

National Cancer Institute

Vilnius, Lithuania

Location

Haukeland universitetssykehus

Bergen, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

Universitetssykehuset i Nord-Norge

Tromsø, Norway

Location

St. Olavs Hospital

Trondheim, Norway

Location

Related Publications (2)

• Horndalsveen H, Haakensen VD, Madebo T, Gronberg BH, Halvorsen TO, Koivunen J, Oselin K, Cicenas S, Helbekkmo N, Aanerud M, Ahvonen J, Silvoniemi M, Bjaanaes MM, Farooqi S, Nebdal D, Dalsgaard AM, Danielsen BK, Borve M, Dalen TS, Ojlert AK, Helland A. Blood-based tumor mutational burden as a biomarker in unresectable non-small cell lung cancer treated with chemoradiotherapy and durvalumab. Front Oncol. 2025 Oct 22;15:1681420. doi: 10.3389/fonc.2025.1681420. eCollection 2025.

  PMID: 41199847 DERIVED

• Langberg CW, Horndalsveen H, Helland A, Haakensen VD. Factors associated with failure to start consolidation durvalumab after definitive chemoradiation for locally advanced NSCLC. Front Oncol. 2023 Jul 5;13:1217424. doi: 10.3389/fonc.2023.1217424. eCollection 2023.

  PMID: 37476372 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Åslaug Helland, Prof, MD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD, Head of Research

Model Details: open, exploratory, multinational, phase 2 trial

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 19, 2020
• Study Start: May 11, 2020
• Primary Completion: May 1, 2025
• Study Completion (Estimated): May 1, 2033
• Last Updated: February 29, 2024

Record last verified: 2024-02

Locations

NO (5); FI (3); LI (1); ES (1)