Study of immune resistance in cancer patients after immunotherapy

Immune Resistance Interrogation Study

Observational University Health Network, Toronto · NCT04243720

This study is trying to understand why some cancer patients don’t respond to immunotherapy while others do, by looking at their tumor and blood samples.

Quick facts

Study typeObservational
Enrollment100 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity Health Network, Toronto Academic / other
Drugs / interventionsimmunotherapy
Locations1 site (Toronto, Ontario)
Trial IDNCT04243720 on ClinicalTrials.gov

What this trial studies

This observational study aims to analyze the differences in genomic, transcriptomic, epigenetic, and immunophenotypic profiles between cancer patients who exhibit primary resistance to immunotherapy and those who initially respond but later progress. Patients who have progressed on immunotherapy will undergo a one-time fresh tumor biopsy, along with serial blood samples, archival tissue (if available), and a stool sample. The study seeks to better understand the biological factors contributing to resistance in order to improve future treatment strategies.

Who should consider this trial

Good fit: Ideal candidates include patients with solid tumors who have progressed on immunotherapy as their most recent line of therapy.

Not a fit: Patients who have not undergone immunotherapy or those with non-solid tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized and effective treatment options for cancer patients who do not respond to immunotherapy.

How similar studies have performed: While there have been studies on immunotherapy resistance, this specific approach focusing on the detailed molecular profiling of resistant patients is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Toronto, Ontario

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions CancerSolid TumorMetastatic CancerImmune ResistanceMolecular ProfilingLiquid BiopsyTumor BiopsyCirculation Tumor DNA
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.