PI-031 - FIRST-IN-HUMAN (FIH) STUDIES FOR ONCOLOGY DRUGS: HEALTHY VOLUNTEERS (HVS) OR PATIENTS WITH CANCER

O. Ivanova¹, R. Abbas¹, Z. Lu¹, X. Chen¹, J. Sheng²; ¹Incyte Corporation, Wilmington, DE, USA, ²Incyte Research Institute, Wilmington, DE, USA.

Background: FIH oncology trials were traditionally conducted in patients with cancer, mainly due to safety concerns with chemotherapy and no efficacy benefits in HVs. There is a growing interest in HV studies for targeted and immuno-oncology therapies. A multifaceted assessment of potential safety concerns, health authority regulations, global drug development strategy, and the complex interplay of the aforementioned factors is required to decide on FIH trials in HVs vs patients with cancer. This abstract summarizes current FIH oncology trial practices and compares the benefits and pitfalls of trials in HVs vs patients.

Methods: We conducted a literature search in the public domain (including PubMed, ClinicalTrials.gov, and regulatory guidance) of FIH oncology or hematology trials in HVs or patients with cancer for interventions including small molecules, monoclonal or bispecific antibodies, and antibody-drug conjugates. Key project management elements, including cost, timeline, and development strategies, were also considered. The pros and cons of conducting FIH studies in HVs vs patients with cancer are summarized.

Results: FIH trials in HVs are primarily for small molecule oncology drugs, mainly as single-ascending dose studies. This approach enables pharmacokinetic (PK) characterization, food-effect, and drug-drug interaction evaluation; early (but limited) safety data collection; and can facilitate formulation changes. A case study of FIH population PK analysis of INCB106385 in HVs illustrates formulation development aided by absorption assessment. Compared with studies in patients, FIH oncology trials in HVs may accelerate its drug development by providing safety and PK data earlier, faster enrollment, and reduced costs. Nonetheless, these benefits should be weighed against the inherent risk of safety without efficacy benefit and the feasibility of collecting pharmacodynamic biomarkers in HVs. Importantly, regional regulatory requirements for oncology drug development vary; the number of FIH studies in HVs may increase in countries/regions with more lenient criteria and faster approval processes.

Conclusion: With emerging scientific data and an evolving regulatory landscape, the practice of conducting FIH trials in HVs continues to advance to optimize clinical outcomes.