Abstract 1696
Background
Early drug development and phase 1 (P1) clinical trials have changed dramatically in the past decade, as targeted therapies and then immune-oncology evolved. Understanding the changing trends in P1 trials allows more targeted resource investment at the site level, but also at the industry level. We describe the changes in the P1 trial landscape in solid tumours over the past decade.
Methods
P1 trials registered on ClinicalTrials.gov to start between 1/1/2009-31/12/2018 were extracted using the parameters: cancer, ≥18 years (yr) old, active, recruiting, completed, (early) P1 and interventional. Of the 7,870 trials identified, 3,031 were excluded on the following basis: not conducted in patients with solid tumours, directed at supportive care, solely involving radiotherapy (RT), testing of a device or procedure or solely involving dietary interventions. The 4,839 eligible studies were categorized by treatment type, tumor type, start date and study location. Studies were independently reviewed by two clinicians.
Results
In the past decade, there was an average increase of 5%/yr in the number of P1 registered, reflected by substantial increases in trials investigating immune-oncology agents (IO) (average increase: 36%/year) and cell therapies (CT) (average increase: 17%/yr). P1 trials using chemotherapy (C) (average decrease: 1%/yr) or targeted therapies (T) (average decrease: 1%/yr) have plateaued. Clinical trials combining IO with T or C or RT increased by an average of 45%/yr. Most P1 studies (41%) enrolled multiple tumour types. Studies frequently involved North American (68.5%), European (29.3%) and Asia Pacific sites (34%). The inclusion of Asia Pacific sites increased most substantially (average increase: 8%/year). P1 Trials Classified by Type of Therapy (2009-2018)Table:
494P
IO1 | C1 | T1 | CT1 | Total | |
---|---|---|---|---|---|
2009-10 | 4% (30) | 39% (324) | 66% (557) | 5% (39) | 839 |
2011-12 | 12% (89) | 36% (276) | 64% (491) | 3% (25) | 767 |
2013-14 | 17% (141) | 32% (258) | 57% (467) | 6% (47) | 814 |
2015-16 | 33% (364) | 29% (320) | 48% (529) | 9% (98) | 1095 |
2017-18 | 44% (581) | 23% (305) | 40% (524) | 11% (140) | 1324 |
Includes P1 trials using a combination of treatments.
Conclusions
The conduct of P1 trials has increased markedly over the past decade, driven by growing interest in IO.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Peter MacCallum Cancer Centre.
Funding
Has not received any funding.
Disclosure
J. Desai: Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bionomics; Research grant / Funding (institution): MedImmune; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy: Eisai; Advisory / Consultancy: Ignyta. B. Tran: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astella; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen-Cilag; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Tolmar; Advisory / Consultancy: Ipsen. All other authors have declared no conflicts of interest.
Resources from the same session
3887 - First Real Life Data on Durvalumab after definitive concomitant ChemoRadiotherapy (cCRT) in unresectable Stage (St) III Non-Small Cell Lung Cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) Temporary Authorization of Use (ATU)
Presenter: Virginie Avrillon
Session: Poster Display session 1
Resources:
Abstract
682 - EGFR Inhibitor Versus Chemotherapy as Adjuvant Treatment for Locally-advanced EGFR-mutant Non-Small Cell Lung Cancer
Presenter: Peng Xie
Session: Poster Display session 1
Resources:
Abstract
2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3300 - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis
Presenter: Daniel SW Tan
Session: Poster Display session 1
Resources:
Abstract
2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Presenter: Xiaohong Wang
Session: Poster Display session 1
Resources:
Abstract
5921 - Definition of an afatinib trough concentration threshold in the treatment of NSCLC
Presenter: Stephane Bouchet
Session: Poster Display session 1
Resources:
Abstract
2852 - A Phase Ib Trial of Neoadjuvant Chemoradiotherapy and Durvalumab(MEDI4736) for Potentially Resectable stage III Non-Small Cell Lung Cancer (NSCLC)
Presenter: Beung chul AHN
Session: Poster Display session 1
Resources:
Abstract
3273 - Low expression of Notch1 and combined Notch1/HES1 are associated with adverse survival factor for limited stage small cell lung cancer
Presenter: Jinsoo Lee
Session: Poster Display session 1
Resources:
Abstract
5141 - Mutational profiling of tumor tissue and sequential plasma illustrates emergent clones during treatment in late stage small cell lung cancer (SCLC)
Presenter: Stephanie Yaung
Session: Poster Display session 1
Resources:
Abstract