The State of Preclinical Modeling for Early Phase Cancer Trials Using Molecularly Targeted Agents with Radiation

Area of Science:

• Oncology
• Translational Cancer Research
• Radiation Oncology

Background:

• Preclinical research is crucial for developing novel cancer treatment combinations.
• Translating laboratory findings into clinical application requires robust justification.
• Combining molecularly targeted agents with radiation therapy presents unique challenges.

Purpose of the Study:

• To evaluate the approaches used by cancer researchers to justify advancing new molecularly targeted agent-radiation combinations into early-phase clinical trials.
• To quantify the characteristics and preclinical data supporting these combination studies.
• To understand the landscape of preclinical support for molecularly targeted agent-radiation combinations.

Main Methods:

• Analysis of unsolicited early-phase clinical trial proposals submitted to the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP).
• Data curation from January 2016 to July 2020.
• Quantification of key characteristics and the proportion of preclinical data provided.

Main Results:

• Characterization of the preclinical data landscape supporting molecularly targeted agent-radiation combinations.
• Identification of common approaches and data types used to justify trial advancement.
• Elucidation of challenges in translating these combinations from preclinical to clinical settings.

Conclusions:

• The study provides insights into the current state of preclinical evidence supporting molecularly targeted agent-radiation combinations in early-phase trials.
• Understanding these approaches highlights challenges at the intersection of precision medicine and radiation oncology.
• This analysis can inform future strategies for preclinical development and clinical translation of combination cancer therapies.