# Evolving or Immutable - Phase I Solid Tumor Trials in the Era of Precision Oncology

## TL;DR

This study examines how phase I solid tumor trials have changed in the precision oncology era, focusing on drug types, trial designs, and patient inclusion criteria.

## Contribution

The paper provides a systematic survey of phase I solid tumor trials from 2010–2020, highlighting trends in drug classes and trial methodologies.

## Key findings

- Targeted therapy and immunotherapy are the most studied drug classes in phase I trials during the precision oncology era.
- Rule-based dose escalation schemes, particularly the 3+3 design, remain the most common despite the shift from chemotherapy to newer therapies.
- Only 40.1% of trials used expansion cohorts, with 46.6% of those defined by genomic selection.

## Abstract

In the era of precision oncology (PO), systemic therapies for patients (pts) with solid tumors have shifted from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). This systematic survey describes features of trials enrolling between 2010–2020, focusing on inclusion criteria, type of dose escalation scheme (DES) utilized, and use of expansion cohorts (ECs).

A literature search identified phase I studies in adults with solid tumors published January 1, 2000 – December 31, 2020 from 12 journals. We included only studies enrolling between 2010–2020 to better capture the PO era. Two reviewers abstracted data; a third established concordance.

Of 10,744 studies, 10,195 were non-topical or enrolled prior to 2010; 437 studies were included. The most common drug classes were TT (47.6%), IO (22%), and CT (6.9%). In studies which reported race, patients were predominantly white (61.7%) or Asian (25.7%), followed by black (6.5%) or other (6.1%). Heterogeneity was observed in the reporting and specification of study inclusion criteria. Only 40.1% of studies utilized ECs, and among the studies which used ECS, 46.6% were defined by genomic selection. Rule-based DES were used in 89% of trials; a 3+3 design was used in 80.5%. Of all drugs tested, 37.5% advanced to phase II, while 10.3% garnered regulatory licensure (for an indication tested in phase I).

In the era of PO, TT and IO have emerged as the most studied agents in phase I trials. Rule-based DES, which are more relevant for escalating CT, are still chiefly utilized.