Reconsidering The 3+3 Dose Escalation In Oncology Studies

By Anne Poli, Jennifer Murphy, and Anna Hertzberg

Numerous product developers are driven by the imperative of swiftly and safely delivering life-saving treatments to patients who have exhausted other options. While the standard 3+3 dose escalation in first-in-human (FIH) clinical trials remains the norm for oncology development, exploring alternative Phase 1 study designs is essential to determining the optimal recommended Phase 2 dose (RP2D) for patients before advancing to later-stage studies.

In recent years, the oncology landscape has witnessed the rise of molecularly targeted agents (MTAs) and immunotherapies, marking a shift away from cytotoxic agents. As this treatment paradigm evolves, researchers are increasingly urged to consider study designs that ascertain the optimal biological dose rather than solely focusing on the maximum tolerated dose (MTD).

In March 2022, the FDA issued the final Guidance for Industry titled "Expansion Cohorts: Use in First-in-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics," offering recommendations for incorporating expansion cohorts within FIH trials. Emphasizing flexibility, safety monitoring, biomarker-driven strategies, and collaborative efforts in study design and execution, the guidance underscores the significance of these approaches. Expansion cohort studies may employ rule-based or model-based approaches, contingent upon trial specifics and objectives, and are advised to target patients with serious oncologic diseases lacking alternative treatments.

Learn more about why incorporating alternative study designs to efficiently determine a safe and optimal RP2D is paramount for clinical research in 2024 and beyond by accessing the full article below.