Evolving or immutable - phase I solid tumor trials in the era of precision oncology

Area of Science:

• Oncology
• Clinical Trials
• Drug Development

Background:

• Precision oncology has shifted cancer treatment from chemotherapy to targeted and immunotherapies.
• Phase I trials are crucial for evaluating novel cancer therapeutics.

Purpose of the Study:

• To systematically analyze phase I clinical trial features in solid tumors during the precision oncology era (2010-2020).
• To assess the utilization of inclusion criteria, dose escalation schemes, and expansion cohorts.

Main Methods:

• Systematic literature search of phase I solid tumor trials published between 2000-2020.
• Inclusion of studies enrolling patients between 2010-2020.
• Data abstraction on drug class, inclusion criteria, dose escalation, and expansion cohorts by multiple reviewers.

Main Results:

• Targeted therapy (47.6%) and immunotherapy (22%) were the most common drug classes.
• Only 40.1% of studies used expansion cohorts, with 46.6% based on genomic selection.
• Rule-based dose escalation (89%), primarily 3+3 designs (80.5%), remained dominant despite the rise of targeted and immunotherapies.

Conclusions:

• Targeted therapy and immunotherapy are now the primary focus of phase I oncology trials.
• The continued reliance on rule-based dose escalation schemes may not be optimal for novel targeted and immunotherapies.
• Further alignment of trial design methodologies with the evolving landscape of cancer therapeutics is warranted.