Recruiting

Immune Resistance

Sponsor:

University Health Network, Toronto

Code:

NCT04243720

Conditions

Cancer

Solid Tumor

Metastatic Cancer

Immune Resistance

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Study Details

Brief 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 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.

Conditions

Cancer

Solid Tumor

Metastatic Cancer

Immune Resistance

Study ID

NCT04243720

Start date

Aug 26, 2020

Status verified date

Jun, 2026

Completion date

Jun, 2027

Anticipated

Primary completion date

Jun, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

100 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

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 ]
  • 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 ]
  • 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 ]
  • 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 ]

Central Contacts and Locations

Central contacts

Celeste Yu

416-946-4501celeste.yu@uhn.ca

Locations

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G2M9

More Information

Sponsor

University Health Network, Toronto

Last update posted

Jun 10, 2026

Last verified

Jun, 2026

Keywords

  • Molecular Profiling
  • Liquid Biopsy
  • Tumor Biopsy
  • Circulation Tumor DNA
  • Epigenetics
  • Microbiome
  • Radiomics
  • Immune Analysis
  • Immunohistochemistry

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University Health Network, Toronto on 2026-06-10.