Immune Resistance Interrogation Study (IRIS)

June 9, 2026 updated by: University Health Network, Toronto
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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Genomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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
Time Frame: Through study completion, up to 4 years
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anna Spreafico, MD, Princess Margaret Cancer Centre
  • Principal Investigator: Lillian Siu, MD, Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 26, 2020

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 20, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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