Clinical trial NCT04243720: Immune Resistance Interrogation Study
Official title: Immune Resistance Interrogation Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cancer
Solid Tumor
Metastatic Cancer
Immune Resistance
Keywords: Molecular Profiling
Liquid Biopsy
Tumor Biopsy
Circulation Tumor DNA
Epigenetics
Microbiome
Radiomics
Immune Analysis
Immunohistochemistry
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2020-01-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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.

Primary outcomes:
measure: Genomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors
timeFrame: Through study completion, up to 4 years
measure: Transcriptomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors
timeFrame: Through study completion, up to 4 years
measure: Immunophenotypic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors
timeFrame: Through study completion, up to 4 years
measure: Epigenetic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors
timeFrame: Through study completion, up to 4 years
Secondary outcomes:
measure: Genomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy
timeFrame: Through study completion, up to 4 years
measure: Transcriptomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy
timeFrame: Through study completion, up to 4 years
measure: Immunophenotyping changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy
timeFrame: Through study completion, up to 4 years
measure: Epigenetic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy
timeFrame: Through study completion, up to 4 years
Other outcomes:
measure: Radiomic changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors
timeFrame: Through study completion, up to 4 years
measure: Radiomic changes associated with subsequent anticancer therapies in patients with advanced solid tumors who have progressed on immunotherapy
timeFrame: Through study completion, up to 4 years
measure: Fecal microbiome changes associated with primary or acquired resistance to immunotherapy given alone or in combination in patients with advanced solid tumors
timeFrame: Through study completion, up to 4 years
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Lillian Siu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Anna Spreafico, MD
role: PRINCIPAL_INVESTIGATOR
References: