Phase I Prognostic Online (PIPO) Tool

Patient selection in phase I clinical trials continues to be a challenge even in the new "era" with immune checkpoints inhibitors (ICIs) and combinations with small molecules or targeted agents (TAs). Phase 1 trialists are more frequently dealing with novel compounds and new trial designs with large expansion cohort, looking for preliminary evidence of anti-tumor activity and safety in different tumor types and disease settings. During these last years, certain phase 1 trials have had registrational value transforming the classical drug development path. Despite these trends, patients recruited in phase 1 trials are mostly refractory to standard-of-care therapies, where quality of life and life expectancy remain a cornerstone for trial selection. The need to balance potential risks of toxicity and benefits of investigational drugs in this particularly vulnerable cancer population is critical. Most phase 1 clinical trials use life expectancy of at least 3 months as a specific inclusion criterion to minimize the chances of clinical deterioration during the dose limiting toxicity (DLT) assessment period. Nevertheless, there is no consensus on how to objectively make this estimation in real practice.

Several prognostic scores have been developed for phase 1 trials. Most are based on overall survival (OS) prediction but not in the specific timepoint of survival rate at 3 months (3m). These scores were developed for patients treated with cytotoxic agents or targeted drugs in phase 1 units of the Royal Marsden Hospital (RMH score) and the MD Anderson Cancer Center (MDACC). Additionally, prognostic scores specifically for ICIs have been designed at Gustave Roussy Hospital, Paris, France, (GRIm-Score) or MDACC (MDA-ICI) while the Lung Immune Prognostic Index (LIPI) score has been validated as a prognostic score not only for ICIs, but also chemotherapy and TAs.

Most recently, the investigators proposed the Phase I prognostic online (PIPO) tool that was developed interchangeably for TAs and ICIs. The PIPO tool avoid dichotomization of continuous or ordinary variables and provide estimation of specific survival probabilities for each patient before enrolment in a phase 1 trial. To better validate the tool, the investigators plan a prospective validation to assess its prognostic capacity in order to be used as a decision support system in clinical practice of drug development units for objectively estimating life expectancy criterion in phase 1 trials.

Inclusion criteria

• Participants must have been enrolled in a VHIO phase 1 clinical trial or phase 2 basket trial included in this study.