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
2066 - Second-line (2L) real-world treatment (tx) patterns and outcomes in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) treated with first line (1L) immuno-oncology (IO) monotherapy (mono tx)
Presenter: Denis Talbot
Session: Poster Display session 1
Resources:
Abstract
5919 - Real-world effectiveness of nivolumab monotherapy after prior systemic therapy in advanced non-small cell lung cancer (NSCLC) in the United States
Presenter: David Stenehjem
Session: Poster Display session 1
Resources:
Abstract
3368 - Pembrolizumab as first-line treatment in NSCLC with PD-L1 ≥50%: Real life results from an all-comer population
Presenter: Nikolaj Frost
Session: Poster Display session 1
Resources:
Abstract
3775 - Patients with metastatic non-small cell lung cancer without molecular alterations or PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Frank Griesinger
Session: Poster Display session 1
Resources:
Abstract
3926 - Impact of second-line (2L) immune checkpoint inhibitors (ICIs) on the treatment (Tx) of advanced non-small cell lung cancer (NSCLC) in a UK centre: a REAL-Oncology analysis from the I-O Optimise initiative
Presenter: Michael Snee
Session: Poster Display session 1
Resources:
Abstract
5068 - First line pembrolizumab for NSCLC with PD-L1 TPS > 50% in a first French real life cohort
Presenter: Karim Amrane
Session: Poster Display session 1
Resources:
Abstract
1182 - Interstitial lung disease induced by immune-checkpoint inhibitors correlates with prognosis of advanced non-small-cell lung cancer patients
Presenter: Teppei Sugano
Session: Poster Display session 1
Resources:
Abstract
2297 - Phase II study to evaluate the peripheral blood mononuclear cell biomarker for nivolumab efficacy on previously treated non-small cell lung cancer subjects (NEJ029B: IMMUNITY-ONE)
Presenter: Yosuke Kawashima
Session: Poster Display session 1
Resources:
Abstract
2739 - Efficacy and safety of nintedanib + docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Updated results of the ongoing non-interventional study (NIS) VARGADO (NCT02392455)
Presenter: Christian Grohe
Session: Poster Display session 1
Resources:
Abstract
1357 - Upfront atezolizumab chemoimmunotherapy-associated Immune-related adverse events in patients with advanced non-small cell lung cancer
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract