A Phase I Study on the Tolerance, Pharmacokinetics and Pharmacodynamics of YL-13027
|ClinicalTrials.gov Identifier: NCT03869632|
Recruitment Status : Not yet recruiting
First Posted : March 11, 2019
Last Update Posted : March 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumor||Drug: YL-13027||Phase 1|
This is a two-part study comprised of a dose escalation part and a dose expansion part.In the dose escalation part single patient cohorts will be dosed until a single related toxicity of Grade ≥ 2 or a Dose Limiting Toxicity (DLT) is observed. If this occurs, the study will switch to a conventional oncology 3+3 design (3 patients per dose cohort, with the potential to add an additional 3 patients if toxicity is observed) and escalation will continue until the maximum tolerated dose (MTD) is reached and a recommended Phase II (RP2D) dose is determined. Once the MTD is established a separate dose expansion part will enroll up total additional 16 patients at the RP2D.
In this clinical trial, YL-13027 is given orally once daily. A treatment cycle is defined as 28 days. YL-13027 was given until disease progression, unacceptable toxicity, or withdrawal from the study. The protocol was initiated with a single-patient cohort, treated with oral YL-13027 60 mg once daily (QD). Subsequent cohorts used a 3+3 design and evaluated doses of 40-320mg QD. Adverse events (AEs) were graded by NCI-CTCAE v5.0. Efficacy was assessed according toRECIST v1.1.
|Study Type :||Interventional|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||dose escalation|
|Masking:||None (Open Label)|
|Official Title:||A Phase I, Single Arm, Open, Single and Multiple Dosing and Incremental Dose Study of YL-13027 to Evaluate the Tolerance, Pharmacokinetics and Pharmacodynamics in Patients With Advanced Solid Tumor|
|Estimated Study Start Date :||March 2019|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||March 2020|
YL-13027 is a selective inhibitor of the beta isoform of transforming growth factor (TGF-β).
YL-13027 for clinical use is presented as a sterile tablets at 10 mg, or 50 mg doses. The drug product is intended for oral administration.Preset cohorts of 3-6 subjects will be enrolled sequentially at doses of 60, 120, 180, 240, 300, and 360 mg/day.
YL-13027 is a new type of TGF-βselective inhibitor which differs structurally from Galunisertib and its analogs, showing high potency against TGF-β, but with markedly improved selectivity. This higher selectivity for TGF-β may decrease the risk of serious infection seen with Galunisertib and especially with duvelisib due to strong immune suppression.Preclinical evaluation has demonstrated improved efficacy and safety for YL-13027 compared to Galunisertib.
- Dose limited toxicities evaluated with NCI-CTC AE v5.0 [ Time Frame: within 28 days after the first dose ]Incidence of dose limited toxicities and associated dose of YL-13027
- Adverse events evaluated by NCI CTCAE v5.0 [ Time Frame: from the first dose to within 30 days after the last dose ]Incidence of adverse events and associated dose of YL-13027
- Plasma concentration of YL-13027 [ Time Frame: within 56 days after the first dose ]This composite endpoint will measure the plasma concentration of YL-13027
- Objective response rate [ Time Frame: within 30 days after the last dose ]the proportion of subjects who have a Complete Response or Partial Response
- Disease control rate [ Time Frame: within 30 days after the last dose ]the proportion of subjects who have a Complete Response or Partial Response
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03869632
|Contact: Hanying Bao, MD,PhD||86 email@example.com|
|Contact: Yuanyuan Xu, M.S.||86 21-51320088 ext firstname.lastname@example.org|
|Shanghai East Hospital||Not yet recruiting|
|Shanghai, Shanghai, China, 200123|
|Contact: Jin Li, PhD email@example.com|
|Contact: Ye Guo, PhD|
|Principal Investigator: Jin Li, PhD|
|Sub-Investigator: Ye Guo, PhD|
|Study Director:||Hanying Bao, PhD||Shanghai YingLi Pharmaceutical Co. Ltd.|