Chimeric Antigen Receptor CAR T Cell Therapies are generating increasing excitement within the scientific community as certain patient populations continue to show very promising responses. However, CAR T therapy presents a set of toxicity challenges such as treatment-induced neurotoxicity, cytokine release syndrome, autoimmune-like sequelae, and other off target effects.

AS T-cells are modified using viral vectors, there are particular regulatory requirements, such as adherence to genetically modified organism (GMO) guidelines that need to be addressed before commencement of clinical trials. Without an efficient study start-up strategy and expansive understanding of regulations, studies run the risk of delay. A negative impact for patient, physician and drug developer. To provide the best chance for patients to be given potentially CAR T breakthrough treatments on clinical trials it is imperative that sponsor’s adopt a bespoke approach towards study activation and patient recruitment that goes beyond traditional models.

ICON has partnered with a major biopharmaceutical company in the clinical development of CAR T for patients with relapsed and/or refractory Multiple Myeloma (BCMA construct) and B-cell Lymphomas (CD19 construct). The novel program, which includes a site activation timeline tracker that couples historical metrics with aspirational targets, is being deployed globally across Phase 1-3 studies. From the site activation timeline tracker, dedicated strategies are implemented at those points where effective communication can leverage earlier study starts. The team’s goal is to reduce start-up time for all sites by 50%. Additionally, ICON’s CAR-T program proactively engages Competent Authorities and Ethics Committees for direct dialogue on behalf of the Sponsor to head off delaying data or queries that can arise with GMO therapies.

The first US site in a Multiple Myeloma study was activated within one month of the final protocol issue, and the first subject was enroled less than two weeks later. In the B-cell lymphoma study, the first patient was screened 10 days after site activation, and apheresed ten days later. For both studies, enrolment occurred well ahead of the originally planned timelines, and start-up timelines have been reduced by 30–50% for all participants. Additionally, collaboration with competent authorities and ethics committees on GMO regulations has provided functional, seamless, real-time support for the sponsor across the operational continuum. To date, there are over 10 sites currently experiencing these reductions in benchmark timelines as a result of the CAR T program, giving studies the momentum they need to provide CAR T treatment options to patients in need.

• Reduced study start-up timelines by 30–50%
• A new approach to resourcing, budgeting and operational strategy
• Adherence to genetically modified organism (GMO) guidelines
• Functional, seamless and real-time support to the sponsor across the operational continuum