Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma

Stomach Neoplasms

Carcinoma, Hepatocellular

Melanoma

Carcinoma, Renal Cell

Mesothelioma

Mesothelioma, Malignant

Endometrial Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Stomach Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Amino Acids

Immune Checkpoint Inhibitors

Pembrolizumab

Tislelizumab

Immunomodulating Agents

Nivolumab

Durvalumab

Atezolizumab

Liver Extracts

Tyrosine Kinase Inhibitors

Tyrosine

Blood will be taken in order to elucidate transcriptomic and proteomic differences (1) pre- and post-ICI treatment commencement; (2) in patients with and without immune-related adverse events.

Blood screening

Archival tumor tissue (FFPE) will be spatially analysed in order to define tissue heterogeneity in tumor samples regarding cancer immune cell transcriptional profiles and correlate it with the occurrence/development of immune-related adverse events.

Tissue screening

Dmitrii Shek, Dr

Bo Gao, Dr

Adnan Nagrial, A/Professor

Matteo Carlino, A/Professor

Golo Ahlenstiel, Professor

"Risk factors of Immune-ChEckpoint inhibitor MEdiated Liver, gastrointestinal, endocrine and skin Toxicity" (ICEMELT) study is a prospective multicenter cohort study, enrolling patients who are scheduled to receive (1) single agent PD1/L1 inhibitor; (2) PD1/L1 inhibitor plus CTLA4 inhibitor; (3) platinum-based chemotherapy + PD1/L1 inhibitor; (4) PD1/L1 inhibitor and tyrosine kinase inhibitor and (5) PD1/L1 inhibitor and vascular endothelial growth factor (VEGF) inhibitor.

This project is based on strong multidisciplinary collaboration between oncologists, gastroenterologists/hepatologists, immunologists and basic scientists affiliated with (1) Western Sydney University, (2) University of Sydney, (3) Western Sydney Local Health District (4) New South Wales Health Pathology, (5) Westmead Institute for Medical Research.

Recruitment sites:

* Blacktown Mt Druitt Hospital.
* Westmead Hospital.

Research samples collection, processing and storage:

* Blacktown Clinical School, Western Sydney University.
* Westmead Institute for Medical Research, the University of Sydney.
* New South Wales Health Pathology.

Potential patients will be identified by study investigators at Oncology clinics. After informed consent, clinicopathological data including patients' demographics, past medical history, cancer staging, relevant anticancer treatment, response/progression and survival will be collected longitudinally.

The following specimens will be collected from all participating patients at baseline (pre-treatment stage):

* Peripheral blood (3 x 10mL EDTA tubes)
* FibroScan (CAP score for elucidating pre-existing liver fibrosis)
* Formalin-Fixed Paraffin-Embedded (FFPE) samples (one block) from core biopsies which is a part of routine care for cancer patients.

The following specimens will be collected after IPI + NIVO therapeutic regimen will be commenced (week 6-9 after ICI-therapy commencement):

• Peripheral blood (3 x 10mL EDTA tubes)

Upon development of potential grade ≥2 irAEs, the following samples will be collected:

* Peripheral blood (3 x 10mL EDTA tubes)
* FibroScan (for patients with hepatic irAEs)
* Tissue samples (if biopsies are collected as per standard of care for patients with immune-mediated colitis who will be required to undergo colonoscopy)

Peripheral blood samples from patients will be collected using 10ml EDTA vacutainer tubes (x3) and processed within 12 hours of collection by research staff at each site. Plasma will be used for miRNA assay. PBMCs will be split into 5 cryotubes and used for flow cytometry and single-cell sequencing.

Consent to the study will allow researchers to access the baseline archive diagnostic FFPE tissue samples. With implementing cutting-edge spatial analysis we aim to elucidate the impact of tumour-infiltrating immune microenvironment on clinical outcomes of ICI therapy.

Fresh tissue samples obtained from patients with severe immune-mediated colitis will be processed to obtain total RNA and immune cells for sequencing and mass spectrometry (CyTOF). In addition, tissue samples will be analysed with in situ spatial profiling technologies to map multi-omic data on subcellular level and to determine its association with the clinical outcomes of cancer immunotherapy.

Risk Factors of Immune-ChEckpoint Inhibitors MEdiated Liver, Gastrointestinal, Endocrine and Skin Toxicity

This objective will be achieved through single-cell sequencing.

In order to ascertain this result, our objective is to utilize spatial transcriptomics and mass spectrometry.

University of Western Sydney

Bristol-Myers Squibb

Western Sydney Local Health District

Professor of Medicine

Spots Global Cancer Trial Database for tissue screening