In the quest to build asset value and secure ongoing investment, biotech and emerging biopharma sponsors frequently rely on key safety indicators from early phase studies to establish dosage for later phase trials. However, this strategy is largely based on the model of identifying the maximum tolerated dose (MTD) for dose selection, which originates from the traditional use of cytotoxic chemotherapies. Consequently, this can often lead to under-characterized doses and schedules for new molecularly targeted and immunotherapeutic agents before progressing to registration trials.

In January 2023, the U.S. Food and Drug Administration (FDA) introduced draft guidelines under Project Optimus on “Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.” The guidelines propose that clinical trials should be designed to compare multiple dosages, assessing not only the efficacy of a drug but also its safety and tolerability, including long-term, cumulative toxicities.

As highlighted at the 2023 ESMO Congress special symposium, “Challenging the status quo of early phase clinical trial design: Project Optimus,” this dose optimization paradigm brings additional challenges to biotech sponsors in terms of increasing required patient numbers, intensifying trial complexity and escalating costs.

Cancer patients’ participation in clinical trials remains low, around six percent. ⁱThe competitive landscape at clinical trial sites, especially in the wake of the pandemic, has further complicated matters. The need for more patients to be enrolled in dose optimization cohorts presents a significant hurdle for sponsors.

In response to this challenge, IQVIA Biotech is actively working to expand the footprint for Phase 1 studies. The goal is to extend these trials beyond specialist academic centers into a wider range of investigator sites. One such initiative is the expansion of IQVIA's Early Phase Oncology Network, a global network of experienced Phase I oncology sites working in close alignment for fast site activation and better patient recruitment. By utilizing pre-identified experienced sites, the timeline for site selection can be reduced, leading to improved operational efficiencies.

Moreover, IQVIA Biotech is dedicated to employing a patient-centric approach in study design. This strategy prioritizes patient comfort and convenience, aiming to alleviate any unnecessary burden on patients. As a result, this can lead to improved enrollment and retention rates in clinical trials. We are also committed to promoting diversity and inclusivity within clinical trials. IQVIA Biotech embeds diversity across planning and execution of clinical trials to boost participation among populations that have historically been underrepresented in such studies.

There is often a call to “keep it simple” in Phase 1 dose evaluation. However, when working with immunotherapeutic and targeted agents, the process of finding the optimal dose acknowledges the additional complexities of working with these novel agents. Tools for randomization may be required to assign patients to different dose levels, and flexible drug formulations will be necessary to allow different doses to be evaluated. The growing focus on evaluating safety beyond the traditional dose-limiting toxicity (DLT) period and the emphasis on understanding lower grade or chronic toxicities in early phase trials necessitates a greater reliance on electronic patient-reported outcomes (ePRO)/ electronic clinical outcome assessments (eCOA) and quality of life tools normally seen in later stage studies.

IQVIA Biotech is equipped to support the implementation of these tools to support more detailed differentiation between dose levels, ensuring a robust and comprehensive trial safety assessments.

A trial with dose optimization cohorts will almost certainly cost more than without, however it will generate additional value in the asset when a smaller company is looking to partner or raise additional funding for Phases 2 and 3. These companies should weigh the financial implications including factors such as net present value. This consideration is crucial in making strategic decisions about the timing of dose optimization cohorts in these trials. Incorporating statistical modelling techniques that make use of both nonclinical and clinical data can greatly enhance the efficiency of study design. Investors in oncology drug development will also need to know the value that will be generated from the initial additional investment required for dose optimization. Understanding this aspect can provide a clearer picture of the potential return on investment and the overall feasibility of the project.

We help our biotech sponsors leverage a deeper understanding of the patient profile and market dynamics throughout the journey of their asset from clinic to commercialization. Ensuring that the clinical trial design carefully considers endpoints that demonstrate value and communicates this information clearly to all stakeholders allows us to help you get your breakthroughs to patients, faster.

In this era of molecularly targeted and immunotherapeutic agents, it is increasingly apparent that more drug is not necessarily always better, and that including dose optimization early in development strategies will provide cancer patients with a better balance of efficacy and tolerability.

At IQVIA Biotech, our goal is to ensure successful trial outcomes while maintaining the highest standards of patient safety and trial integrity. We are prepared to meet the demands of the evolving clinical trial landscape, providing solutions that not only address the challenges of today, but also pave the way for future advancements in oncology drug development.

Want to learn more about how IQVIA Biotech is helping sponsors navigate this new dose optimization paradigm? Contact us.

ⁱ DOI: 10.1200/JCO.2020.39.28_suppl.74 Journal of Clinical Oncology 39, no. 28_suppl (October 01, 2021) 74-74. Published online September 21, 2021. https://ascopubs.org/doi/abs/10.1200/JCO.2020.39.28_suppl.74