CancerIRISNCT04243720
Immune Resistance Interrogation Study
An observational study of Cancer and Solid Tumor, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Solid Tumor, Metastatic Cancer
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 26 Aug 2020to Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a diagnosis of solid tumor malignancy who progressed on immunotherapy as their most recent line of therapy.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G2M9
About this study
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.
Read the 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.
- Conditions
- Cancer, Solid Tumor, Metastatic Cancer, Immune Resistance
- Keywords
- Molecular Profiling, Liquid Biopsy, Tumor Biopsy, Circulation Tumor DNA, Epigenetics, Microbiome, Radiomics, Immune Analysis, Immunohistochemistry
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through study completion, up to 4 years
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through study completion, up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2020
- Study start26 Aug 2020
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lillian Siu, MD, Principal investigator, Princess Margaret Cancer CentreAnna Spreafico, MD, Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04243720
- Sponsor's protocol ID
- IRIS
- Other IDs
- CAPCR ID
- Acronym
- IRIS
- Status last verified
- Jun 2026
- First submitted
- 20 Jan 2020
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Resistance Interrogation Study
- ClinicalTrials.gov ID
- NCT04243720
- Acronym / sponsor ID
- IRIS / IRIS
- Conditions
- Cancer, Solid Tumor, Metastatic Cancer, Immune Resistance
- Keywords
- Molecular Profiling, Liquid Biopsy, Tumor Biopsy, Circulation Tumor DNA, Epigenetics, Microbiome, Radiomics, Immune Analysis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 26 Aug 2020 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 28 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a diagnosis of solid tumor malignancy who progressed on immunotherapy as their most recent line of therapy.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
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.
4 secondary outcomes
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lillian Siu, MD principal investigator
Princess Margaret Cancer Centre
Anna Spreafico, MD principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer and Solid Tumor, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Celeste Yu (416-946-4501 ext. 5281, celeste.yu@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.