Immune-related adverse events (irAEs) are one of the leading causes affecting success rates of immunomodulatory drugs requiring a concerted multistakeholder effort across the drug development process—especially within the nonclinical phase. One of the ways in which the imSAVAR consortium aims to help improve the research and development process and bring a degree of alignment is by creating a Model Grading System through an iterative manner and by leveraging on the imSAVAR Stakeholder Community. A key aspect of imSAVAR is continuing dialogue with patient stakeholders to keep the imSAVAR research agenda patient-centred and maximise outcomes for patients. In an effort to better elucidate inclusion of patient preferences within nonclinical assessment of immunomodulatory therapies, we co-designed a Workshop on “Integrating Patient Preferences in Nonclinical Assessment of Immunomodulatory Therapies – Shifting the Paradigm” with representatives of Melanoma Patient Network Europe (MPNE), Lung Cancer Europe (LuCE), CML Advocates Network and Patvocates—all of whom are part of WECAN which is an informal network of leaders of cancer patient umbrella organisations active in Europe. This online imSAVAR Stakeholder Workshop took place on 26 & 27 January 2022 with a programme composed of various key opinion leaders representing stakeholders such as: Patient Advocates, Clinicians, Toxicologists, Immunologists and Researchers.
The first part of the Workshop focused on presenting the landscape of how immune-related adverse events (irAEs) linked to immune-oncology therapies are managed in clinical practice, complemented by the state of the art in translational safety assessments (i.e., nonclinical models and biomarkers) for predicting these irAEs and challenges and limitations associated with both. This was followed by sharing of patient perspectives on irAEs across different cancers, emphasising not only the heterogeneity in patient preferences regarding treatment outcomes but the risk-benefit trade-offs and treatment choices they struggle with. To culminate, the IMI PREFER evidence-based recommendations on when and how to elicit patient preferences provided an exemplar methodology on capturing the patient voice in medical product decision making, which although deemed vital by most stakeholders lacks guidance.
The second part of the Workshop involved pooling together the captured insights in a multistakeholder deliberation on how to embed patient preferences in the research and nonclinical development phase to better address patient unmet needs. Despite the often diverging stakeholder views on treatment outcomes, there was convergence regarding the need to improve tools to better predict safety and efficacy of immunotherapies—largely stemming from the numerous novel advanced therapies and combinations available, improved long term survival of patients across cancers but offset by an ever growing array of complex and unpredictable irAEs. With patients prioritising long-term and acute toxicities besides just severe toxicities, efforts are needed in modelling for their prediction as well. Whilst managing the risk of immune toxicities is already challenging, it is further intensified by the need to balance the effects of immune toxicity treatments on diminishing the efficacy of cancer treatments. Well curated data linking nonclinical development with clinical experience and utilising “patient reported phenotypes” as a priority setting tool for research were stressed as key considerations to address the issues laid out to reach a balanced immune safety and efficacy profile. Although the pursuit of integrating patient preferences within nonclinical safety assessment strategies for immunomodulatory therapies may be unprecedented, its realisation—with all healthcare innovation being a complex endeavour—demands a collaborative approach.