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Clinical-pathological correlates to response to immune checkpoint inhibitors in metastatic melanoma

A 2019/2020 Summer Studentship research project

This work will help determine correlations between clinical characteristics and response/toxicity to nivolumab and pembrolizumab. In particular, this will help in a larger project to define if NZ patients receiving these agents have similar or different outcomes to those reported in the literature. Additionally, there may be opportunity to explore correlation between clinical data and novel measures of antibody (drug) and anti-antibody (anti-drug antibody) concentrations.

Student: Tim Bridgeman
Supervisors: R. Matthew Strother, MD, FRACP, Professor Bridget Robinson, Associate Professor Margaret Currie, Barry Hock (Scientific Officer & Honorary Research Fellow)
Sponsor: Cancer Society Ashburton Group

Introduction

Treatment of metastatic melanoma has changed dramatically in the past 2 years in New Zealand with the funding of the anti-PD1 checkpoint inhibitors nivolumab and pembrolizumab. These agents are associated with response rates in clinical trials approaching 70% in the first year, and 40% appear to be long term responders. A significant proportion of patients (approximately 20%) do however develop severe adverse reactions. The reasons underlying the wide variation in patients’ responses to these therapies are unclear. Recent studies have suggested exposure to antibiotic and immunosuppressive therapies may impact on effectiveness. Additionally there is some evidence that the occurrence of immune related side effects may have prognostic value. At this time, there are limited studies correlating clinical and pathological characteristics to either response or toxicity, particularly in “real world” hospital settings. Additionally, very limited data correlates these outcomes to non-clinical laboratory measures of inflammation or drug concentration. CDHB Oncology has been collecting blood on patients receiving PD-1 inhibitors over the past two years, allowing exploration of novel laboratory studies with clinical correlates.

Aims

  1. To populate a database of patients with metastatic melanoma being treated with anti-PD1 inhibitors, and explore correlations between clinical observations, exposure to additional therapies, laboratory analyses and outcomes
  2. explore clinical activity in patients receiving checkpoint inhibitors in CDHB, and compare to national reports.

Method

An ongoing cohort trial recruiting patients being treated with standard of care immune checkpoint inhibitors for metastatic melanoma. As per routine clinical practice, patients undergo routine blood collection, toxicity and clinical assessment, and 3 monthly CT scans. Additional blood is collected prior to each administration for measurement of anti-drug antibodies and measurement of the immune checkpoint inhibitor. Descriptive statistics will be used to explore relationships between clinical measures and laboratory measures.

Student researcher’s component of the study

The mentorship team will help the student set-up a database (likely in RedCap). The student will be asked to fill in the database with clinical data and non-clinical data collected on all patients treated with PD-1 inhibitors. Student will be welcome to participate in the clinical evaluation and enrolment of any new patients that arise during the period of project (1-2 per week). Descriptive statistics will be performed under the mentorship of the research team. There will be opportunity to work with the research nurses collecting specimens and possibly participate in the assays measuring drug and anti-drug antibodies.

Student Prerequisites

Medical student preferable, comfort with spreadsheets. Willingness to learn some statistics and programming.

How to apply

Email Matthew.strother@cdhb.health.nz