In the ever-evolving landscape of oncology drug development, first-in-human (FIH) and early phase trials are pivotal milestones that set the stage for future successes. These critical stages serve as the launch point in a company’s pursuit of drug development, offering an early glimpse into the safety and efficacy profile of a novel investigational product. Dynamic by nature, these trials necessitate holistic planning to ensure successful implementation and delivery.

Optimizing Study Protocols

Efficiency is key when it comes to study protocols. By leveraging advanced tools and data-driven methodologies, we can significantly reduce patient burden while simultaneously decreasing the likelihood of protocol amendments. This analytical and proactive approach not only streamlines processes but also accelerates timelines without compromising safety or putting efficacy endpoints at risk.

Streamlining Study Protocols: Study protocols form the backbone of clinical trials, defining the procedures, assessments and data collection points. Optimizing these protocols involves several key considerations:

• Patient-Centric Design: We prioritize patient well-being by minimizing unnecessary procedures and assessments. By carefully selecting endpoints and including only assessments targeted at these, we reduce the burden on participants while maintaining scientific rigor.
• Minimizing white space: Leveraging advanced technologies leads the study and Sponsor to quicker insights that ensure rapid decision-making and reduced downtime between trial phases.
• Adaptive Designs: Embracing adaptive designs enables mid-course adjustments based on accumulating data. Whether it’s dosing schedules, sample size re-estimation, or endpoint modifications, adaptive protocols enhance flexibility and responsiveness.

Understanding Project Optimus’ Impact

Project Optimus is a transformative initiative and reform within early phase oncology trials, challenging the bias that more cytotoxicity is better to treat the cancer, or that doses can be optimizes in later stages of development. The influence of Optimus extends beyond scientific aspects to operational effects, fostering an environment where adaptive designs are encouraged. Let’s delve deeper into its impact:

• Balancing Safety with Efficacy. Because immunotherapies and targeted agents, as compared to traditional cytotoxic agents, have unique mechanisms of actions, it is critical to consider safety and biologic activity during dose selection, and to design early phase studies to collect and assess dynamic data, rather than a pure Maximum Tolerated Dose approach.
• Integration of Patient Reported Outcomes (PROs). PROs provide a systematic and quantitative assessment of expected symptomatic adverse events and their impact on patient’s daily lives. By integrating PROs earlier into the design process, we can achieve more effective treatments and improve patient outcomes by avoiding dose interruptions or modifications that negatively impact patient well-being.
• Modeling and simulation using multiple datasets. To increase the chance of successful identification of the optimal dose in a trial, modeling and simulation can provide critical insights with multiple datasets being used to maximize efficacy measurements. For example, assessing overall response rate together while assessing supporting evidence from PD biomarkers can help pinpoint an optimized dose level and schedule.

Enhancing Clinical Trial Representation

Ensuring clinical trials enroll patient populations that are representative of the intended treatment population is an important scientific and ethical imperative. To help enhance representativeness within clinical trial participants in the United States, bi-partisan legislation was passed by U.S. Congress in 2022, which requires thoughtful assessment of patient population demographics and strategies that broaden participation while maintaining rigorous compliance standards. At IQVIA, we aim to ensure:

• Inclusive Trial Design: We actively seek diverse patient populations, considering factors like age, sex, race, ethnicity, and comorbidities. Inclusive trials yield robust data that better represent real-world patients.
• Cultural Competence: Understanding cultural nuances is crucial to ensuring patient awareness of clinical research and fostering participation among historically underrepresented populations in trials. We collaborate with investigators and communities to ensure culturally sensitive trial design, conduct, recruitment and retention.
• DEPICT Act Compliance: The FDA’s DEPICT Act strengthens diversity in clinical trials. Our strategies align with these guidelines, promoting equitable access and participation.

Conclusion

As we navigate these initial phases of oncology trial design and execution, success hinges on our ability to adapt swiftly without losing sight of core objectives: safety, efficacy and inclusivity. The next frontier in early phase oncology trials beckons us to explore uncharted territories, armed with innovative strategies and unwavering commitment to advancing patient care.

Author Bios:

Erin Finot, Vice President, Immuno-Oncology and Cell & Gene Therapy (CAGT) at IQVIA Biotech, brings extensive expertise to pioneering approaches in early-phase clinical trials. With a passion for patient-centric research, Erin drives innovation and excellence in oncology drug development.

Matt Simmons, Senior Director, Oncology Strategy at IQVIA Biotech brings three decades of clinical research experience supporting sponsors and understanding their needs early in drug development to create effective clinical trial strategies. By collaborating across teams, he ensures development plans meet expectations and drive successful outcomes.

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