Abstract 2273
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.
Clinical trial identification
Editorial acknowledgement
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.
Resources from the same session
2182 - Evaluating the prevalence of the expression of PD-L1 in NSCLC specimens with short-duration formalin fixation using IHC 22C3 pharmDx
Presenter: Keiichi Ota
Session: Poster Display session 1
Resources:
Abstract
5255 - [18F]-FDG PET/CT in predicting PD-L1 status in nasopharyngeal carcinoma
Presenter: Liang Zhao
Session: Poster Display session 1
Resources:
Abstract
4910 - Expression of PD-L1 in Chinese Patients with Common Cancers
Presenter: Min Zheng
Session: Poster Display session 1
Resources:
Abstract
4227 - The clearance of EGF by tumor-associated macrophages is suppressed by chemotherapeutic agent cisplatin
Presenter: Irina Larionova
Session: Poster Display session 1
Resources:
Abstract
5222 - VHIO-300 and a thousand one nights, a tale of Precision Medicine
Presenter: Ginevra Caratù
Session: Poster Display session 1
Resources:
Abstract
5668 - Matched Whole-Genome Sequencing and Whole-Exome Sequencing with Circulating Tumor DNA (ctDNA) Analysis are complementary modalities in clinical practice
Presenter: Robin Imperial
Session: Poster Display session 1
Resources:
Abstract
5772 - Exploring the role of genes associated with familial cancer syndromes on the development of multiple primary tumors
Presenter: Atanaska Mitkova
Session: Poster Display session 1
Resources:
Abstract
4784 - Doxorubicin resistance: early and advanced tumors can use two different strategies based on initial and profound abnormalities in microRNA expression signature
Presenter: Volodymyr Halytskiy
Session: Poster Display session 1
Resources:
Abstract
3456 - From tumor transcriptomes to underlying cell type proportions to better predict prognosis and response to treatments
Presenter: Yuna Blum
Session: Poster Display session 1
Resources:
Abstract
4976 - Optimization of automated germline DNA extraction from non-tumoral formalin-fixed paraffin embedded (FFPE) tissues
Presenter: Omar Youssef
Session: Poster Display session 1
Resources:
Abstract