scholarly journals Trends of Phase I Clinical Trials of New Drugs in Mainland China Over the Past 10 Years (2011–2020)

2021 ◽  
Vol 8 ◽  
Author(s):  
Chen Chen ◽  
Ning Lou ◽  
Xin Zheng ◽  
Shasha Wang ◽  
Haizhu Chen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Innovation Policy ◽  
Mainland China ◽  
Annual Growth Rate ◽  
Therapeutic Area ◽  
Phase I Clinical Trials ◽  
The Past ◽  
Innovative Drugs

Background: In recent years, the number of clinical trials initiated in China has increased rapidly. The aim of this study was to overview the changing landscape of phase I clinical trials in mainland China from 2011 to 2020.Methods: We analyzed phase I clinical trials registered on 3 websites including the Chinese Clinical Trial Registry, ClinicalTrials.gov, and the China National Medical Products Administration Center for Drug Evaluation platform.Findings: A total of 2,842 phase I clinical trials were posted from January 1, 2011, to December 31, 2020. The overall number of clinical trials for innovative drugs was 1,497, accounting for half of all the phase I clinical trials (53%). Among these 1,486 innovative drug clinical trials, 924 were newly tested drugs with an average annual growth rate of 59%. Biological drug research increased significantly from 22.6% during 2011–2015 to 33.3% during 2016–2020. These principal investigators (PIs) of these clinical trials were mainly from Beijing (n = 871), followed by Shanghai (n = 496) and Jiangsu (n = 281). As for the therapeutic area of phase I clinical trials, cancer took up the most percentage of all the clinical trials (35%), followed by infectious disease (9%), nervous system disease (9%), etc. Most phase I clinical trials are conducted on healthy volunteers (n = 1,642, 57.8%), some cancer drugs are conducted in patients with cancer (n = 846, 29.8%), and only a few clinical trials were conducted in the elderly (n = 7). Among these clinical trials of the newly tested innovative drugs, the first in human (FIH) clinical trials accounted for 82% (744), and the First in Chinese (FIC) clinical trials only took up 18% (167). Only a small number of drugs could be made the transition to phase II (n = 207, 22%). In addition, despite the number of newly tested drugs during 2011–2015 (n = 163) was much less than that in 2016–2020 (n = 761), the percentage of drugs that could enter into phase II clinical trials in 2011–2015 (34%) was higher than that in 2016–2020 (20%).Conclusion: In the past 10 years, the development of phase I clinical trials has achieved great progress in mainland China due to the novel design and drug innovation policy. Nevertheless, future efforts are needed to make for improving the phase transition success rate of innovative drugs.

Identification of a predictive biomarker and two pharmacodynamic biomarkers to ADG106 treatment, a novel anti-CD137 agonist antibody, in phase I clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14505-e14505
Author(s):  
Li Zhang
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Predictive Biomarker ◽  
Phase I Trials ◽  
Tumor Shrinkage ◽  
Target Engagement ◽  
Phase I Clinical Trials ◽  
Phase Ii Trials ◽  
Pharmacodynamic Biomarkers

e14505 Background: ADG106 is a fully human agonistic anti-CD137 monoclonal IgG4 antibody that mediates anti-tumor activities via unique mechanisms of action. Here we provide safety and efficacy updates from our phase I trials and report the findings of a predictive biomarker and two pharmacodynamic biomarkers which correlate with patients’ clinical responses to ADG106 treatment and demonstrate target engagement, respectively. Methods: Formalin fixed and paraffin embedded (FFPE), blood and plasma specimens were collected from 92 patients enrolled in our phase I trials. We measured expression across a panel of protein biomarkers in FFPE specimens using three highly sensitive detection technologies: multiple immunohistochemical (IHC) staining of protein expression, the BD Multitest 6-color TBNK reagent for profiling immune cell subpopulations, and the MSD-ECL electrochemiluminescence assay for detection of soluble CD137. Objective tumor responses were determined using RECIST v1.1 for solid tumor patients and Lugano classification for lymphoma patients. Results: As of November 30, 2020, ADG106 has demonstrated a favorable safety profile and efficacy in the phase I clinical trials with a disease control rate of 56%. From a retrospective analysis of 28 pretreatment FFPE specimens, we identified a predictive biomarker that correlated with tumor shrinkage upon ADG106 treatment. We identified four biomarker positive specimens from two patients with lymphoma and two with solid tumors. Three out of four biomarker positive patients achieved greater than 30% tumor shrinkage after 3mg/kg or 5mg/kg ADG106 treatment. One biomarker positive patient with stable disease received a low dose ADG106 treatment at 0.5mg/kg during dose escalation. None of the 24 biomarker negative patients showed significant clinical response. A tissue microarray study confirmed expression of this predictive biomarker in a variety of tumor types suggesting a broad indication for ADG106 therapy. Our biomarker studies also demonstrated target engagement with increased NK cell proliferation and soluble CD137 upon ADG106 treatment. Analysis of safety, efficacy, PK and PD data allowed us to select a recommended dose for the upcoming phase II study. Conclusions: We identified a biomarker predictive of response to antitumor CD137 blockade by ADG106, as well as demonstrated the involvement of NK cells in ADG106 mediated anti-tumor activities. In upcoming phase II trials, we plan to enrich for populations expressing this predictive biomarker to demonstrate a clinical benefit to ADG106 therapy further validating early biomarker-based patient stratification. We will also explore the potential of selecting patients for combination treatment with anti-PD-1 therapies. Clinical trial information: NCT03802955.

The changing face of phase I protocols: A closer look at study requirements

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3061-3061
Author(s):  
B. S. Craft ◽  
R. Kurzrock ◽  
R. Herbst ◽  
K. Culotta ◽  
C. Stewart ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Medical Oncology ◽  
Current Phase ◽  
Recent Experience ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Phase Ii Trials ◽  
Versus Phase

3061 Background: We have studied our recent experience in the MDACC Clinical Translational Research Center (CTRC), the Phase I Program, and the Dept. of Thoracic/Head & Neck Medical Oncology to compare the extent of regulatory and other requirements for current phase I and II cancer clinical trials. Methods: We developed a comprehensive database, together with a Microsoft Excel spreadsheet matrix to analyze the number and extent of diagnostic and therapeutic requirements for each protocol. We then examined the demands for pharmacokinetic (PK) sampling as well as electrocardiography (ECG) in the first cycle of a protocol as a surrogate for study complexity. Results: Since October, 2002, 250 protocols have been conducted in the CTRC; 54.6% were Phase I clinical trials. We reviewed 65 trials, approximately one quarter of the total. Of these, 48 were phase I trials carried out by the Phase I Program. For comparison, we identified 17 phase II trials managed by the Dept. of Thoracic/Head & Neck Medical Oncology during the same time period. In the phase I trials there were significantly more PKs (mean ± SE = 16.69 ± 1.93) than in the phase II trials (mean ± SE = 1.82 ± 1.17) (p<0.0001). Similarly, there were more ECGs in the phase I versus phase II trials (4.46 ± 1.18 vs. 1.41 ± 0.35; p=0.017). Conclusions: Pharmacokinetic collection and ECG monitoring in Phase I trials are complex and labor-intensive. In addition, they represent only a small portion of time-intensive requirements, with increasingly complicated correlates and monitoring (physical exams, imaging, etc.). Successful and accurate Phase I clinical trials require resources and commitment for research infrastructure considerably greater than later phase studies. No significant financial relationships to disclose.

scholarly journals Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

2006 ◽  
Vol 24 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Andrew J. Vickers ◽  
Joyce Kuo ◽  
Barrie R. Cassileth
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Phase Ii ◽  
Dose Finding ◽  
Phase Iii ◽  
High Dose ◽  
Free Text ◽  
Phase Ii Trials ◽  
Off Label

Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.

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