Clinical Benefit and Biomarker Analysis of Combination of PD-1/PD-L1 Immune Checkpoint Inhibitors and Radiotherapy

Study Overview
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Brief Summary
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Inhibitors of the programmed cell death protein 1 (PD-1)/PD-L1 immune checkpoint signaling pathway are already approved in the treatment of various tumor entities in relapsed or metastatic stages. Different exploratory trials suggest that the combination of radiotherapy and PD-1/PD-L1 inhibitors is highly effective, especially in oligometastatic stages and if all lesions are treated with ablative radiotherapy. In addition, the role of predictive biomarkers is becoming increasingly important for future therapy algorithms. First data, also from our group, indicate clearly that dynamic changes of immune cells and their activation markers in the peripheral blood (immune matrix) can be used as predictive biomarkers. During the planned STICI-02 trial predictive immune matrix derived from the STICI01 trial (NCT03453892) will be validated in the groups of patient suffering from HNSCC (palliative), NSCLC (separately palliative and adjuvant) and other solid tumors (including in particular esophageal carcinomas, urothelial and renal carcinomas, small cell bronchial carcinomas and squamous cell carcinomas of the skin [depending on the current drug approval]). Within the framework of scientific accompanying projects, the predictive value of markers in tumor tissue and of pattern radiomics analyses will be analyzed accompanying the immunophenotyping in peripheral blood. The side effects

Official Title
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Clinical Benefit and Biomarker Analysis of Combination of PD-1/PD-L1 Immune Checkpoint Inhibitors and Radiotherapy in NSCLC, HNSCC and Other Solid Tumors

Conditions
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HNSCC, NSCLC, Esophageal Cancer, Urothelial Carcinoma, Renal Cell Carcinoma, Squamous Cell Carcinoma of the Skin, Small Cell Bronchial Carcinomas

Intervention / Treatment
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* Other: Conventional Therapy acc. to prevailing clincal approved schemes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treatable for HNSCC (palliative), NSCLC (separately palliative and adjuvant) or other solid tumour Indication for system therapy with a PD-1/PD-L1 inhibitor according to clinical standards Patients without or with radiation of one or more metastases Age at least 18 years Exclusion Criteria: Melanoma patients Fertile patients who refuse effective contraception during study treatment Persistent drug and/or alcohol abuse Patients not able or willing to behave according to study protocol Patients in care Patients that are not able to speak German Patients which are imprisoned according to legal or governmental order Both gender are included into the study, a maximum age was not defined.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Trial cohort<br>The study cohort consist of patients suffering from HNSCC (palliative), NSCLC (separately palliative and adjuvant) and other solid tumors (including in particular esophageal carcinomas, urothelial and renal carcinomas, small cell bronchial carcinomas and squamous cell carcinomas of the skin [depending on the current drug approval]) which will be treated with ICI (PD-1/PD-L1) and potential radiation of metastases at Department of Radiation Oncology of Universitätsklinikum Erlangen. | Other: Conventional Therapy acc. to prevailing clincal approved schemes<br>* The study is observational. The treatment-plan of the underlying disease remains unchanged. The treatment of the patient is according to the prevailing clinical approved schemes at the respective entities. Blood will be drawn from patients at several time points during and after RT and ICI for detailed immunomonitoring of the patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overallsurvival | Prospective investigation of the survival of the patients. | From inclusion till death of subject or up to 5 years, whichever came first. | 
| Longitudinal Immunophenotype | Longitudonal Immunophenotyping of the patients: Detection of about 30 distinct immune cell (sub)types together with their activation markers during treatement. | Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first. | 
| Predictors in pattern recognition analyses | Identification of possible predictors in pattern recognition analyses from clinical imaging data sets. | Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first. | 
| Immune-associated side effects | Detection of immune-associated side effects | Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of adverse events according to NCI CTAE (v4.0) | The adverse effects of Immunecheckpoint and Radiotherapy is recorded by official questionaire | From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, or till change to conventional treatment , whichever came first, assessed up to 5 years. | 
| Progression free survival | survival of the patient without progression of malignant disesase | From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, whichever came first, assessed up to 5 yeras | 
| Treatment response (according to RECIST and iRECIST criteria) | RECIST and iRECIST criteria will used to analyse the response of the patient to the respective treatement | From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, whichever came first, assessed up to 5 years | 
| Attempt to establish an immune matrix of responding/non-responding patients | Analysis of clincal, MRI and imunnologic, molecular data to develop an biomarkermatrix with processes of machine learning | The analyses are conducted at time points before (day 0) and before every prescription of ICI (every 14 to 21 days) till progression or end of study up to 5 years or till change to conventional treatment without ICI. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Radiotherapy