489PHigh performance of serial tumour biopsies in first in human (FIH) phase I trials

Abstract Background In the current oncology new drug development, evaluation of the proof of concept (POC) in first in human trials (FIH) is essential. The serial tumor biopsy (i.e., pre-treatment biopsy and post-treatment biopsy) has supported us investigating POC, and had substantial potential to explore the target indication as well as optimizing the developmental strategy. However, regardless of protocol requirement, it has been often invasive to cancer patients and resulted in uninspired outcome, due to its tumor location or patients’ condition. We evaluated our performance of serial tumor biopsies in FIH trials. Methods From July 1995 to April 2019, we retrospectively reviewed the FIH trials conducted at our center and analyzed the acquisition rate of serial tumor biopsies as well as the pathological diagnostic accuracy. The acquisition rate was calculated as the number of samples taken per the number of samples required in their protocol. Results Of phase I trials (n = 147) including 46 FIH trials, 12 FIH trials (n = 80) since 2015 were mandatory for serial tumor biopsies (including single tumor biopsy in 3 trials). Out of the 108 biopsies taken, the primary tumor site were as follows; colorectal (n = 20), lung (n = 16), pancreas (n = 11), breast (n = 5) and others (n = 28). In regards to technical procedure, ultrasound-guided needle biopsy (n = 46), bronchoscopy (n = 33), percutaneous biopsy (n = 19), CT-guided needle biopsy (n = 8) and endoscopy (n = 2) were performed. The biopsy sites were liver (n = 37), lung (n = 24), lymph nodes (n = 24), skin and soft tissue (n = 17) and others (n = 6). The acquisition rate of tumor biopsies mandatory in the 12 FIH trials was 96.4% (95%CI: 91.2 – 98.6%), and 79 out of 85 samples could achieve definite pathological diagnosis with the accuracy rate of 92.9% (95%CI: 85.4-96.7%). Paired pathological diagnosis were also available with the rate of 88.5% (95%CI: 71.0-96.0%). The major reason missing biopsy (n = 19) was the study termination due to the disease progression (68.4%). Two adverse events of grade 2 were experienced during biopsies. Conclusions This analysis demonstrated the outstanding performance of serial tumor biopsy in FIH trials. We consider it properly contributes to the global standard in early drug development. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure T. Shimizu: Advisory / Consultancy: Takeda Oncology; Honoraria (self): Ono Pharmaceutical; Honoraria (self): ONO Pharma Taiwan CO.; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Research grant / Funding (self): Takeda Oncology; Research grant / Funding (self): PharmaMar; Research grant / Funding (self): Bristol-Myers Squibb Japan; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): SymBio Pharmaceuticals; Research grant / Funding (self): Five Prime Therapeutics; Research grant / Funding (self): 3D Medicine; Research grant / Funding (self): Chordia Therapeutics; Research grant / Funding (self): AbbVie; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Novartis. N. Yamamoto: Advisory / Consultancy, Research grant / Funding (self): Eisai; Advisory / Consultancy, Research grant / Funding (self): Takeda; Advisory / Consultancy: Otsuka Pharmaceutica; Speaker Bureau / Expert testimony, Research grant / Funding (self): Bristol-Myers Squibb Japan; Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (self): Lilly Japan; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ono Pharmaceutical; Speaker Bureau / Expert testimony, Research grant / Funding (self): Chugai Pharmaceutical; Research grant / Funding (self): Taiho Pharmaceutical; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Novartis; Research grant / Funding (self): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Kyowa Hakko Kirin; Research grant / Funding (self): Bayer; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Janssen Pharma; Research grant / Funding (self): MSD; Research grant / Funding (self): MERCK. All other authors have declared no conflicts of interest.