Abstract 593P
Background
Drug development follows a progressive transition from preclinical studies to clinical practice across the multiple phases of clinical research. We aimed at describing the step-by-step evolution of a homogenous class of agents, cyclin-dependent kinases inhibitors, with a focus on phase (ph) I trials, a springboard for clinical development.
Methods
Trials registered on ClinicalTrials.gov were extracted using the following search parameters: palbociclib (PD0332991; Ibrance), ribociclib (LEE011; Kisquali), and abemaciclib (LY2835219; Verzenio), with a limit through the end of 2019.
Results
The analysis included 383 studies, conducted from 2004 to 2019, investigating palbociclib (53%), ribociclib (24%), abemaciclib (20%), or >1 of those drugs (3%). Trials were breast specific in 47% (181), non-breast in 53% (202); sponsored by industry in 38% (146), by a non-profit organization or academia in 30% (114), by their co-participation in 32% (123). A trend over time was registered in favour of breast specific studies (p=0.002) and academia involvement (p < 0.0001). Overall, 125 trials were ph1 (33%), 40 ph1-2 (10%), 152 ph2 (40%), 3 ph2-3 (1%), 35 ph3 (9%), 7 ph4 (2%), 4 EAP (1%). In particular, among 125 ph1 trials, 30 enrolled healthy participants (24%), 30 enrolled patients with multiple solid tumours (24%), 30 breast (24%), 10 brain (8%) and 25 other tumour types (20%). Out of 125 ph1 studies, 75 (60%) were sponsored by industry, 22 (18%) by a non-profit organization or academia, 28 (22%) by their co-participation. The designated primary endpoint was dose limiting toxicity in 32 (26%), maximum tolerated dose in 24 (19%), recommended phase two dose in 4 (3%), pharmacokinetics in 34 (27%), safety in 25 (20%) and in 8 cases (6%) a biological endpoint. The intervention assignment followed a crossover model in 16 (13%), parallel in 38 (30%), sequential in 9 (7%), single arm in the remnant 62 cases (49%). Of note, 15 ph1 trials (12%) were randomized. Year of phase I trial start ranged from 2004 to 2019, with a median of study initiation in 2016.
Conclusions
Longitudinal analysis of clinical trials may help to optimize drug development and to improve strategies for the future cooperation between industry and academia.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Cardone: Travel/Accommodation/Expenses: Servier. A. Gravina: Travel/Accommodation/Expenses: Pfizer. F. Perrone: Honoraria (self): Daiichi Sankyo; Honoraria (self): GSK; Honoraria (self): MSD; Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): AstraZenca; Travel/Accommodation/Expenses: Bayer. M.C. Piccirillo: Honoraria (self): Daiichi Sankyo; Honoraria (self): GSK; Honoraria (self): MSD; Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Travel/Accommodation/Expenses: Bayer. All other authors have declared no conflicts of interest.