Immune Resistance Interrogation Study (IRIS)

This is a prospective research study which will include patients who have progressed on immunotherapy as their most recent line of therapy. This study aims to characterize whether patients who fail to respond to immunotherapy versus patients who respond initially but after a period of time progress demonstrate different genomic, transcriptomic, epigenetic, immunophenotyping profiles. Patients will have a one-time fresh tumor biopsy. Serial blood samples (total amount of blood drawn may not exceed the lesser of 50 mL or 3 mL/kg in an 8 week period), archival tissue (if available) and one stool sample will be collected.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Solid Tumor; Metastatic Cancer; Immune Resistance

Detailed Description

Although there has been some success with the use of immunotherapy treatments specifically antibodies that block the programmed death 1 receptor (PD1/L1), the majority of cancer patients either fail to respond (primary resistance) or respond initially but progress after a period of time (acquired resistance) when treated with immunotherapy agents. The hypothesis being tested is whether patients who have primary versus acquired resistance to immunotherapy demonstrate different genomic, transcriptomic, immunophenotypic and/or epigenetic profiles.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Celeste Yu; Phone Number: 5281 416-946-4501; Email: celeste.yu@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Recruiting
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of solid tumor malignancy who progressed on immunotherapy as their most recent line of therapy.

Description

Inclusion Criteria:

• Patients with a histological or cytological diagnosis of solid malignancies, with at least one tumor lesion amenable to core needle biopsy and consent to such a procedure.
• Patients must have progressed on immunotherapy (defined as anti-PD1/PD-L1 antibodies given as monotherapy or as part of a combination therapy) as their most recent line of therapy. Patients will be classified into two groups: 1) those who benefitted from immunotherapy with either complete response (CR), partial response (PR) or prolonged stable disease (SD) lasting at least 6 months with subsequent progression or who had disease progression after at least 12 weeks from the last dose of immunotherapy in the adjuvant setting (i.e. acquired resistance), 2) those whose disease is primary refractory to immunotherapy with disease progression at their first on-treatment imaging, those who benefitted from immunotherapy with stable disease (SD) but progressed in <6 months or those that had progressive disease earlier than 12 weeks from the last dose of immunotherapy in the adjuvant setting.
• Patients must be of good performance status, ECOG 0-1, for subsequent anticancer therapy, with either standard treatment or within the context of a clinical trial.
• Patients must be ≥ 18 years old.
• Patients must have provided voluntary written informed consent.

Exclusion Criteria:

• Any condition that could interfere with a patient's ability to provide informed consent such as dementia or severe cognitive impairment.
• Any contraindication to undergoing venipuncture.
• Any condition that, in the opinion of the Investigator, would interfere with patient safety, or evaluation of the collected specimens and interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Immune Resistance Interrogation Study (IRIS); Patients with a histological or cytological diagnosis of solid malignancies. Patients must have progressed on immunotherapy as their most recent line of therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors	The genomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years
Transcriptomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors	The transcriptomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years
Immunophenotypic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors	The immunophenotypic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years
Epigenetic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors	The epigenetic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy	The genomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years
Transcriptomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy	The transcriptomic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years
Immunophenotyping changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy	The immunophenotypic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years
Epigenetic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy	The epigenetic parameters for radiomic imaging analysis will be derived from patients' routine CT scans to study changes in radiomic signatures during treatment.	Through study completion, up to 4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors	Dynamic changes in radiomic signatures of tumors between commencement of systemic treatment and disease progression will be analysed from serial CT scans (normally performed at base line and approximately every 2-3 months thereafter until disease progression).	Through study completion, up to 4 years
Radiomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy	Tumor radiomic signatures will be used to study how phenotypic characteristics of tumors change during systemic therapy and how these signatures correlate with genomic, transcriptomic, immunophenotypic and epigenetic signatures	Through study completion, up to 4 years
Fecal microbiome changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors	DNA extraction will be performed and subjected to Shotgun sequencing. Bioinformatic analysis will be performed to determine microbial taxa composition (operation taxa units - OTU's) and diversity, including abundance plots at class, genus and species levels, alpha diversity (Rarefaction curve, Shannon curve, Rank Abundance curve) and beta diversity ((Un)weighted unifrac distance, PCoA) plots.	Through study completion, up to 4 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Anna Spreafico, MD, Princess Margaret Cancer Centre; Principal Investigator: Lillian Siu, MD, Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; Immunohistochemistry; Liquid Biopsy; Epigenetics; Molecular Profiling; Radiomics; Tumor Biopsy; Circulation Tumor DNA; Immune Analysis
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: IRIS (Alias Study Number); CAPCR ID (Other Identifier: 19-6224)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No