A Phase I Study on the Tolerance, Pharmacokinetics and Pharmacodynamics of YL-13027
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|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 (Clinical Trial)|
|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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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.|