Immune Profiling of Stage III Non-small Cell Lung Cancer Patients Treated With Concurrent Chemoradiation and Adjuvant Durvalumab: A Prospective Observational Phase II Trial

NCT ID: NCT04432142

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2025-12-01

Brief Summary

Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC (non-small cell lung cancer) patients. Identifying the effect of the treatment on immune cells and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers.

Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers.

This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.

Detailed Description

Even with the addition of durvalumab to concurrent chemoradiation, approximately only half of the patients are alive at 3 years, and more have progressed already, either locally or distant. Not much is known regarding to identification of patients that will benefit from adjuvant durvalumab, or regarding resistance to adjuvant durvalumab after chemoradiation. Most data on immunotherapy resistance come from metastatic patients treated with monotherapy PD-(L)1 antagonists. Depending on PD-L1 expression level, 10-44% of patients respond well to PD-(L)1 antagonists. The majority of patients are either unresponsive, or experience a tumor recurrence after achieving an initial response. The development of individual immunological treatment strategies (e.g. selection of best treatment: mono- or combination ICI, ICI combined with chemotherapy, or the addition of radiotherapy) is hampered by the lack of knowledge in the best timing, sequencing, and dosing of all modalities and the lack of optimal biomarkers for monitoring the treatment response. This highlights the need of clear biomarkers that can be used to select the best treatment for each individual patient and predict whether patients will benefit from adjuvant immunotherapy. Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC patients. Identifying the effect of the treatment on immune cells (e.g. T-, B-, NK-cells, dendritic cells, macrophages) and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers.

Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers.

This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Proton

Patients receiving proton therapy

No interventions assigned to this group

Photon

Patients receiving photon therapy in 4 fractions or less

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Pathological diagnosis of adequately staged (according to standard practice using chest-CT, FDG-PET, brain imaging MRI/CT) NSCLC
• Participant is willing and able to give informed consent for participation in the trial
• Male or female, aged 18 years or above
• Scheduled to receive one of the following two therapeutic strategies:

• Concurrent chemotherapy and radiotherapy with photons (60 Gy in 30 fractions of 2 Gy) in patients with stage III NSCLC
• Concurrent chemotherapy and radiotherapy with protons (60 Gy in 30 fractions of 2 Gy) in patients with stage III NSCLC
• Is able and willing to comply with all trial requirement

Exclusion Criteria

• Mixed non-small cell lung cancer with other histologies such as small cell lung cancer
• Not able to comply with the study protocol
• Less than 18 years' old
• Pregnancy or not able to comply with adequate contraception in women with child baring potential
• Previous radiotherapy to the chest for benign or malignant conditions, including radiation for breast cancer
• Previous malignancy treated with chemotherapy, immune therapy or radiotherapy (irrespective of when this happened)
• Previous malignancies treated with surgery only are allowed if 2 years or more before inclusion in the present study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maastricht Radiation Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dirk De Ruysscher, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastro

Locations

Maastricht Radiation Oncology (MAASTRO clinic)

Maastricht, , Netherlands

Countries

Netherlands

Other Identifiers

IPON-1

Identifier Type: -

Identifier Source: org_study_id