Successful adaptation to complex dose escalation

In 2015, ICON was selected by a mid-size biotech company to support a Phase 1 dose escalation and cohort expansion study of an immune checkpoint inhibitor, in patients with advanced solid tumors. Mid-study, the sponsor was acquired by a large pharma company to which ICON has efficiently supported the transition to the evolving sponsor business model and operations.

The sponsor presented ICON with frequent shifts in strategy for the Part 1 escalation cohorts, including changes in prioritisation for the [at times] competing Part 1 cohorts (e.g., monotherapy, combination therapy, triple combo therapy, special interest patients, etc.). Despite these challenges, the ICON team stayed flexible with site and amendment coordination, collaborated to optimise strategies, exemplified strong cross-functional leadership to maintain overall high-quality monitoring, and successfully met all data deliverables. Throughout the timeline changes, ICON project managers modeled enrollment scenarios to assist the sponsor in their drug development planning.

The primary study challenges related to frequent changes to patient population, enrollment timelines (including protocol amendments), cohort prioritisation, timing for Part 2 expansion (impacting Part 2 start-up), and short notice on data cleaning deliverables to meet evolving development objectives.

The primary study challenges related to frequent changes to patient population, enrollment timelines (including protocol amendments), cohort prioritisation, timing for Part 2 expansion (impacting Part 2 start-up), and short notice on data cleaning deliverables to meet evolving development objectives.

The ICON team worked with the sponsor to ensure 30-day notice on all data cleaning deliverables to adequately prepare and plan with sites. Changes in study population (e.g., anti-PD1/L1 vs IO-naïve) for new cohorts were addressed by conducting thorough feasibility with active sites, consulting with ICON scientific leadership on therapeutic landscape assessment, and modeling enrollment rate scenarios for new populations by region. ICON recommended additional sites when needed and adjusted site start-up and enrollment timelines based on aforementioned evaluations.

Through heightened site communication and an IRT system, ICON effectively and successfully managed the slot assignments across this highly complex cohort design. Enrollment for the overlapping Part 2 expansion cohorts was achieved ahead of the agreed timelines. The team also rigorously orchestrated data entry and cleaning efforts across the Part 1 and Part 2 cohorts to achieve cleaning deliverables for IB updates, cohort review meetings, and DMC meetings. These were achieved with high quality and within the required timelines.

As a result of the solutions noted above as implemented by ICON, enrollment for the various cohorts (and Part 2 expansion) has been met in advance or within all agreed timelines. Data cleaning activities and deliverables have been met with great collaboration, transparency, and most importantly with utmost quality within the agreed timelines. As a result, the client has been able to identify the optimal dose level and indication for continued testing of their investigational product.

“Thanks for making our project a success!”
Sponsor Director, Clinical Operations

“I deeply value your collaborative, flexible, and proactive approach to execute high quality projects with efficiencies. We’ve certainly shared and overcome challenges together, but we’ve celebrated even more successes, thanks to your strong leadership and support.”
Sponsor Clinical Development Director, Oncology