Practical consideration for successful sequential tumor biopsies in first-in-human trials

Area of Science:

• Oncology
• Clinical Pharmacology
• Translational Medicine

Background:

• Sequential tumor biopsies are vital for proof of concept in first-in-human (FIH) trials of investigational new drugs.
• Evaluating the success rates and identifying factors influencing sequential tumor biopsy acquisition in FIH trials is critical for drug development.

Purpose of the Study:

• To assess the success rates of sequential tumor biopsies in FIH trials.
• To explore strategies for enhancing the success of sequential tumor biopsies in FIH trials.

Main Methods:

• Retrospective review of sequential tumor biopsies from 17 out of 52 FIH trials (2015-2020), involving 138 patients.
• Defined success as acquisition of viable tumor cells (single biopsy) and from both specimens (sequential biopsies).
• Analyzed correlations between adverse events, timing of imaging assessment, and biopsy success.

Main Results:

• Pretreatment and on-treatment biopsy success rates were high (98.6% and 94.2%), but sequential biopsy success was lower (70.3%).
• Adverse events and the timing of the first imaging assessment (after vs. before on-treatment biopsy) significantly impacted sequential biopsy success.
• Primary reasons for failure included patient refusal (often due to disease progression) and absence of tumor cells in specimens.

Conclusions:

• Sequential tumor biopsies in FIH trials have a notable failure rate, primarily due to patient refusal and specimen inadequacy.
• Scheduling the first imaging assessment after the on-treatment biopsy is proposed to improve the success rate of sequential tumor biopsies.
• Optimizing biopsy protocols is essential for robust proof-of-concept data in early drug development.