Protocol YY-20394-001 is a phase I open-label, first in human, dose escalation study to assess the tolerability, pharmacokinetics (PK) and efficacy of YY-20394 in patients with relapse or refractory B cell malignant hematological tumor.
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 ≥ 3 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 12 patients at the RP2D. In this clinical trial, YY-20394 is given orally once daily. A treatment cycle is defined as 28 days. YY-20394 was given until disease progression, unacceptable toxicity, or withdrawal from the study. The protocol was initiated with a single-patient cohort, treated with oral YY-20394 20 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 v4.0. Efficacy was assessed according to IWG-NHL and CLL consensus response criteria.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
YY-20394 is a new type of PI3K-δ selective inhibitor which differs structurally from idelalisib and its analogs, showing high potency against PI3Kδ, but with markedly improved selectivity (\>1,000-fold selectivity for PI3K-δ versus PI3Kγ). This higher selectivity for PI3Kδ may decrease the risk of serious infection seen with idelalisib and especially with duvelisib due to strong immune suppression.Preclinical evaluation has demonstrated improved efficacy and safety for YY-20394 compared to idelalisib.
Peking Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGJiangsu Province Hospital
Nanjing, Jiangsu, China
NOT_YET_RECRUITINGHematology Hospital of Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
RECRUITINGDose limited toxicities evaluated with NCI-CTC AE v4.0
Incidence of dose limited toxicities and associated dose of YY-20394
Time frame: within 28 days after the first dose
Adverse events evaluated by NCI CTCAE v4.0
Incidence of adverse events and associated dose of YY-20394
Time frame: from the first dose to within 30 days after the last dose
Plasma concentration of YY-20394
This composite endpoint will measure the plasma concentration of YY-20394.
Time frame: within 56 days after the first dose
Objective response rate
the proportion of subjects who have a Complete Response or Partial Response
Time frame: within 30 days after the last dose
Disease control rate
the proportion of subjects who have a Complete Response or Partial Response
Time frame: within 30 days after the last dose
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