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
5638 - Incidence of Vascular Thromboembolism Events in Cancer Patients Receiving Immunotherapy: A Single Institution Experience.
Presenter: Laura Gutiérrez Sainz
Session: Poster Display session 1
Resources:
Abstract
5182 - High Incidence of Venous Thromboembolic Events (VTE) in Patients with Diffuse Large B-Cell Lymphoma.
Presenter: Alaa Abufara
Session: Poster Display session 1
Resources:
Abstract
1504 - Weight Loss over Time in Non-Small Cell Lung Cancer: Results from a Landmark Analysis of 800+ Prospectively-Treated Patients
Presenter: Jennifer Le-rademacher
Session: Poster Display session 1
Resources:
Abstract
3972 - The prognostic significance of preoperative nutritional status in resected pancreatic ductal adenocarcinoma (PDAC).
Presenter: Salvatore Paiella
Session: Poster Display session 1
Resources:
Abstract
2313 - Impact of Timing and Technique of Gastrostomy Placement on the Outcome of Patients (pts) with Head and Neck Cancer (HNC)
Presenter: M Julia Lostes Bardaji
Session: Poster Display session 1
Resources:
Abstract
5219 - Clinical & nutritional determinants of quality of life in patients with incurable cancer
Presenter: Louise Daly
Session: Poster Display session 1
Resources:
Abstract
4075 - Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer
Presenter: In Gyu Hwang
Session: Poster Display session 1
Resources:
Abstract
4159 - Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts).
Presenter: Ilaria Trestini
Session: Poster Display session 1
Resources:
Abstract
1210 - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy
Presenter: Emilien Billon
Session: Poster Display session 1
Resources:
Abstract
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract