Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Antineoplastic Agents, Immunological

* Durvalumab at a fixed dose of 1,500 mg as an IV infusion over 1 hour, on day 1, to be repeated every 4 weeks (Q4W) for a maximum of 12 cycles
* Thoracic radiation therapy (TRT): hypofractionated thoracic radiotherapy consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks (+9 days)

* Durvalumab at a fixed dose of 1,500 mg as an IV infusion over 1 hour, on day 1, to be repeated every 4 weeks (Q4W) for a maximum of 12 cycles
* Thoracic radiation therapy (TRT): conventional fractions of 30 x 2 Gy (60 Gy) within 6 weeks (+9 days)

Durvalumab Injection [Imfinzi]

Conventionally fractionated TRT consisting of 30 x 2 Gy (60 Gy) within 6 weeks

Thoracic Radiotherapy (TRT) conventionally

Hypofractionated TRT consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks

Thoracic Radiotherapy (TRT) hypofractionated

Farastuk Bozorgmehr, Dr. med.

Johanna Riedel, Dr. rer. med.

Farastuk Bozorgmehr, Dr.

This is a randomized, open-label, multicenter, phase II trial investigating the combination of thoracic radiotherapy plus Durvalumab in patients with locally advanced, unresectable NSCLC (stage III) that are unfit for chemotherapy (e.g. due to age and/or frailty).

This trial investigates the feasibility and treatment efficacy when combining durvalumab treatment with either conventionally fractionated (CON-group) or hypofractionated thoracic radiotherapy (HYPO-group) in previously untreated NSCLC stage III patients prone to radiotherapy only.

A safety lead-in phase with stop-and-go design will precede full enrollment into the HYPO-group.

Tumor tissue as well as blood and stool samples will be collected for future biomarker analysis.

It is hypothesized that TRT combined with concurrent durvalumab administration in patients with unresectable stage III NSCLC, who are not amenable to sequential radio-/chemotherapy

1. is safe and feasible,
2. will improve treatment efficacy by a synergistic effect of checkpoint inhibition and the photon-induction of immunostimulatory pathways.
3. will have an effect on the immunological characteristics of the tumor, the microenvironment, and the systemic immune response, such as upregulation of PD-L1 or secretion of stimulatory cytokines and recruitment and priming of immunocompetent cells, which might then mediate the "abscopal effect" beyond the irradiated targets.

Durvalumab treatment and Thoracic Radiotherapy

Thoracic Radiotherapy Plus Durvalumab in Elderly and/or Frail NSCLC Stage III Patients Unfit for Chemotherapy

Thoracic Radiotherapy Plus Durvalumab in Elderly and/or Frail NSCLC Stage III Patients Unfit for Chemotherapy - Employing Optimized (Hypofractionated) Radiotherapy to Foster Durvalumab Efficacy

Vulnerability assessment based on the G8-screening questionnaire and its association to survival and outcome

Toxicity, defined by the occurence of treatment-related pneumonitis grade ≥ 3

Objective response evaluated at 12 weeks (3 months) after first durvalumab administration according to RECIST 1.1 criteria

Occurence of treatment-related AEs and SAEs according to CTCAE V5.0

Frequency of abnormal values of laboratory parameters

Duration of Clinical Benefit (Duration of Complete Response (CR), Partial Response (PR), Stable Disease (SD)) according to RECIST 1.1

Time from the date of allocation / randomization to the date of first observed metastatic lesion (investigator assessment according to RECIST 1.1) or death from any cause

time from the date of treatment allocation to the date of death

Descriptive sub-group analyses of efficacy in relation to PD-L1 expression levels (\<°1% vs ≥°1%)

Spots Global Cancer Trial Database for durvalumab injection [imfinzi]