Clinical trial NCT06536257: Personalised Immunotherapy Platform
Official title: Personalised Immunotherapy Platform (PIP) - Implementation of a Predictive Model of Response to Immunotherapies in Melanoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Melanoma
Cutaneous Squamous Cell Carcinoma
Basal Cell Carcinoma
Merkel Cell Carcinoma
Solid Tumor
Keywords: Biomarker
Predictive
Immunotherapy
Multi-omic
Tumour mutation burden
Gene expression
Tissue imaging
Machine learning
Multiplex immunofluorescence
Immune checkpoint inhibitors
Quantitative pathology
Lead sponsor: Melanoma Institute Australia
Sponsor class: OTHER
First posted: 2024-08-02
Enrollment: 1000
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 melanoma, non-melanoma skin cancer, non-melanoma solid tumours eligible for treatment with immunotherapy(ies)

Brief summary: This is a non-interventional study to prospectively test a suite of predictive biomarker models of immunotherapy resistance in patients with melanoma, non-melanoma skin cancers and other solid tumours. The study will evaluate the documentation, processes, accuracy and utility of the predictive biomarker model in clinical practice.

Detailed description: The Personalised Immunotherapy Program (PIP) is a multicenter biomarker discovery and validation program of multi-omic biomarker based predictive models which aim to identify patients with immunotherapy resistant disease. PIP developed predictive models in retrospective setting, with validation within a prospective clinical observational study.

Immune checkpoint inhibitors targeting the cytotoxic T-cell lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) receptors have revolutionised the treatment of advanced melanoma, resulting in long-term durable responses and a 5-year overall survival of 52% with combination immunotherapy. However, clinical benefit is not universal, and half of these patients do not respond. Therefore, there is an urgent need for clinically validated biomarkers which can identify patients who are at high risk of not responding to standard-of-care immunotherapies and determine which emerging clinical trial agent is most appropriate for a particular patient's disease.

Researchers performed mutation, gene expression and tumour immune profiling on tumour biopsies from melanoma patients treated with anti-PD-1 monotherapy or combined anti-PD-1 and anti-CTLA-4 therapy. From this dataset PIP has developed predictive models to identify patients with immunotherapy resistant disease.

The subsequent PIP-PREDICT is a prospective clinical study that enrols advanced cancer patients who are eligible to receive approved immunotherapies. PIP testing and biomarker reporting is used to screen potential patients. Each patient enrolled in the study receives an individual PIP Biomarker Report, which is presented as part of the established Biomarker Multidisciplinary Team (MDT) meeting of clinical oncologists, pathologists, molecular biologists, trials nursing, PIP, and biospecimen staff on a fortnightly basis.

PIP-PREDICT has a primary goal of determining the accuracy of biomarker predictions from PIP prospectively within oncology clinics. Secondary goals include assessing the feasibility of biomarker assay workflows within diagnostic providers, conducting a cost-benefit ratio analysis, evaluating the effect of biomarker reports on treatment selection within multidisciplinary teams (MDTs), and performing a post-implementation analysis of personalised immunotherapy biomarker reports in treatment decision making.

Eligibility criteria: MELANOMA:

Inclusion Criteria:

1. Written informed consent to participation for the use of tumour tissue, blood and stool and collection of standard clinical data.
2. Histologically confirmed resected stage II (at high risk of recurrence of disease), III or stage IV melanoma (including cutaneous, mucosal, acral, subungual, uveal or unknown primary melanoma) and unresectable Stage III or IV melanoma
3. Eligible to receive immunotherapy
4. Availability of a melanoma tissue sample which was obtained at surgery and where no systemic treatments (e.g. adjuvant treatment) were administered between sample procurement and proposed PIP testing
5. Patients who have received adjuvant or neoadjuvant systemic therapy in the past are eligible if they have had recurrence after neoadjuvant or adjuvant therapy has been completed and the biopsy represents this relapsed disease
6. RECIST version 1.1 measurable disease.
7. Tissue sample must be representative of the whole tumour and therefore excision biopsies are preferred over core biopsies.
8. A life expectancy over 6 months.
9. Prior treatment with BRAF (B-Raf proto-oncogene) / MEK (mitogen-activated protein kinase) inhibitors are acceptable, providing the other eligibility criteria are met.
10. If a patient has had prior radiotherapy for melanoma, the biopsy to be used for the biomarker test must be from an area that was not within the radiotherapy field.

Exclusion Criteria:

1. Patients will be excluded if they have had a positive test result for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection. If receiving treatment and from HCV for at least one year, patients are allowed to participate. No new testing is required for the sole purpose of this pilot phase. Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). No new testing is required

NON-MELANOMA:

Inclusion Criteria:

1. Written informed consent to participation for the use of tumour tissue and collection of standard clinical data
2. Histologically confirmed cancer and eligibility to receive immunotherapy treatment.
3. Availability of a tissue sample where no systemic treatments were administered between sample procurement and proposed PIP testing
4. If treatment has been administered since the last tissue sample was obtained, a new biopsy should be planned for routine testing or clinical trial screening, where a portion of the sample can be used for the predictive assay. No new biopsies are required for the sole purpose of this study.
5. Patients who have received adjuvant or neoadjuvant systemic therapy in the past are eligible if they have had recurrence after neoadjuvant or adjuvant therapy has been completed and the biopsy represents this relapsed disease.
6. Have clinically detectable disease defined as one of more of the following:

   * RECIST measurable. Lesions situated in a previously irradiated area are considered measurable if RECIST-defined disease progression since radiotherapy has been demonstrated in such lesions, OR,
   * Positron Emission Tomography (PET) avid, OR,
   * Clinically evident disease: photographically, detectable on CT or palpable, OR
   * Clinical status measured by observable and diagnosable signs or symptoms.
7. The tissue sample must be representative of the whole tumour and therefore excision biopsies are preferred over core biopsies.
8. A life expectancy over 6 months.
9. Prior treatment with targeted therapies are acceptable, providing the other eligibility criteria are met.
10. If a patient has had prior radiotherapy for melanoma, the biopsy to be used for the biomarker test must be from an area that was not within the radiotherapy field

Exclusion Criteria:

1. Patients will be excluded if they have had a positive test result for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection. If receiving treatment and from HCV for at least one year, patients are allowed to participate. No new testing is required for the sole purpose of this pilot phase. Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). No new testing is required

Primary outcomes:
measure: Assessment of the accuracy of predictive test results in melanoma
timeFrame: 6 months
Secondary outcomes:
measure: Assessment of the inaccuracy of predictive test results
timeFrame: 6 months
measure: Evaluation of a test request form - completion rate
timeFrame: 2 years
measure: Analysis of potential barriers to complete a test request form
timeFrame: 2 years
measure: Evaluation of accessible data in medical records for completion of a test request form
timeFrame: 2 years
measure: Evaluation of a test request form from clinician feedback via qualitative surveys
timeFrame: 2 years
measure: Conduct qualitative surveys to evaluate a test result report from consumers' viewpoint
timeFrame: 1 year
measure: Qualiaitive evaluation of a test result report from consumers' viewpoint
timeFrame: 1 year
measure: Conduct qualitative surveys to evaluation of a test result report from the clinicians' viewpoint
timeFrame: 2 years
measure: Qualiaitive evaluation of a test result report from clinicians' viewpoint
timeFrame: 2 years
measure: Evaluation of the predictive model workflow on result completion
timeFrame: 2 years
measure: Evaluation of the predictive model workflow on result delivery
timeFrame: 2 years
measure: Evaluation of the predictive model workflow turnaround timeframes
timeFrame: 2 years
measure: Evaluation of the predictive model workflow delays
timeFrame: 2 years
measure: Evaluation of the predictive model workflow processes
timeFrame: 2 years
measure: Availability of suitable tissue for the predictive model testing protocol
timeFrame: 2 years
measure: Data quality for the predictive model testing protocol
timeFrame: 2 years
measure: A cost analysis of the predictive model testing protocol
timeFrame: 2 years
measure: Evaluation of the predictive test report in shaping clinician treatment decision making
timeFrame: 1 year
measure: Evaluation of the impact of predictive test result in shaping clinician treatment decision making
timeFrame: 2 years
measure: Concordance of clinician treatment decision making with predictive test results
timeFrame: 2 years
measure: Discordance of clinician treatment decision making with predictive test results
timeFrame: 2 years
measure: Exploratory evaluation of potential new biomarkers of immunotherapy response or resistance in blood and stool samples
timeFrame: 5 years
measure: Evaluation of potential new biomarkers of immunotherapy response or resistance in blood and stool samples on the accuracy of the predictive model
timeFrame: 5 years
measure: Assessment of the accuracy of predictive test results in non-melanoma skin cancer and non-melanoma tumours
timeFrame: 6 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Sydney
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
affiliation: Melanoma Institute Australia
name: James Wilmott, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gide TN, Paver EC, Yaseen Z, Maher N, Adegoke N, Menzies AM, Pires da Silva I, Wilmott JS, Long GV, Scolyer RA. Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies. Oncoimmunology. 2023 Oct 4;12(1):2261248. doi: 10.1080/2162402X.2023.2261248. eCollection 2023.
citation: Mao Y, Gide TN, Adegoke NA, Quek C, Maher N, Potter A, Patrick E, Saw RPM, Thompson JF, Spillane AJ, Shannon KF, Carlino MS, Lo SN, Menzies AM, da Silva IP, Long GV, Scolyer RA, Wilmott JS. Cross-platform comparison of immune signatures in immunotherapy-treated patients with advanced melanoma using a rank-based scoring approach. J Transl Med. 2023 Apr 13;21(1):257. doi: 10.1186/s12967-023-04092-9.
citation: Adegoke NA, Gide TN, Mao Y, Quek C, Patrick E, Carlino MS, Lo SN, Menzies AM, Pires da Silva I, Vergara IA, Long G, Scolyer RA, Wilmott JS. Classification of the tumor immune microenvironment and associations with outcomes in patients with metastatic melanoma treated with immunotherapies. J Immunother Cancer. 2023 Oct;11(10):e007144. doi: 10.1136/jitc-2023-007144.