Safety, Tolerability and Pharmacokinetics Study of KPG-818 in Hematological Malignancies Subjects
|ClinicalTrials.gov Identifier: NCT04283097|
Recruitment Status : Recruiting
First Posted : February 25, 2020
Last Update Posted : May 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hematological Malignancies||Drug: KPG-818||Phase 1|
This is a Phase 1, multicenter, open-label, multiple-ascending dose study to evaluate the safety, PK, and preliminary clinical activity of KPG-818 as a single agent in adult subjects with selected hematological malignancies. The study center(s) will be in the US.
After providing informed consent, subjects will be assessed for study eligibility at the Screening visit (Days -28 to -1). Cohorts of 3 to 6 subjects per dose level will be given escalating doses of KPG-818 during Days 1 to 21 of each 28-day cycle orally until progressive disease (PD), unacceptable toxicity, the subject withdraws, or any other study withdrawal criterion is met. The 5 planned dose escalation cohorts will be 2, 5, 10, 20, and 30 mg followed by dose expansion. The dose of KPG-818 for the first cohort will be 2 mg/day. The highest dose level which may be tested is 30 mg KPG-818. Dose escalation will follow a 3+3 design and dose-limiting toxicity (DLT) will be assessed during the 28-day DLT evaluation period. The Safety Monitoring Committee (SMC) will be responsible for dose escalation decisions, including whether to modify the dose escalation based on the DLT observations or determine RP2D. Escalation to the Maximal Tolerated Dose (MTD) is not appropriate if activity plateaus at a lower dose.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||56 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Dose escalation will based on a 3+3 design followed by dose expansion. Dose-limiting toxicity will be assessed during the 28-day DLT evaluation period. Subjects who exit the study for reasons other than DLT prior to completion of the 28-day evaluation period will be replaced to ensure an adequate safety assessment at each dose level.|
|Masking:||None (Open Label)|
|Masking Description:||This is a open label phase 1 study.|
|Official Title:||A Phase 1, Multicenter, Open-label, Multiple-ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of KPG-818 in Subjects With Hematological Malignancies|
|Actual Study Start Date :||May 15, 2020|
|Estimated Primary Completion Date :||December 30, 2021|
|Estimated Study Completion Date :||December 30, 2021|
KPG-818 dose escalation
KPG-818 is a novel lenalidomide analog and a next generation of immunomodulatory agents. KPG-818 is structurally similar to Celgene's new investigational drug, CC-220, but with much greater cereblon (CRBN) binding affinity. KPG-818 is potent in inhibiting proliferation of hematological cancer cells growth both in vitro and in vivo. The First-in-Human phase I clinical study of KPG-818 has demonstrated that KPG-818 has a good PK profile and a broad safety window.
Other Name: KPG-818 capsules
- Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Up to 6 months of treatment ]Number of Treatment-Emergent Adverse Events(TEAE), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and changes from baseline in laboratory parameters, vital signs, and ECG.
- Recommended Phase 2 Dose (RP2D) [ Time Frame: Up to 28-day of treatment ]Maximum tolerated dose defined as the highest dose level at which 33% or less subjects experience DLT as defined by the protocol.
- PK profile of KPG-818 [ Time Frame: Up to 28-day of treatment ]Cmax, time of the maximum observed plasma concentration (Tmax), AUC0-t, AUC from time zero extrapolated to infinity (AUC0-∞), AUC within a dosing interval (AUC0-τ), apparent total plasma clearance (CL/F), apparent total plasma clearance at steady-state (CLss/F), apparent volume of distribution (Vz/F), apparent volume of distribution at steady-state (Vss/F), and t1/2.
- Preliminary clinical activity [ Time Frame: Up to 6 months of treatment ]Objective response rate (ORR), disease control rate (DCR), time to response, duration of response (DOR), progression-free survival (PFS), event-free survival (EFS), and transplantation rate (TR). Responses are evaluated based on International Myeloma Working Group (IMWG) Uniform Response Criteria (for MM), Lugano Classification 3 (for lymphoma), International Workshop Group on CLL (iwCLL) Response Criteria, and according to the Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia lymphoma (ATL).
- Biomarkers of KPG-818 [ Time Frame: Up to 6 months of treatment ]Aiolos and Ikaros in peripheral blood mononuclear cell (PBMC)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04283097
|Contact: Yong Guo, MDfirstname.lastname@example.org|
|Study Director:||Yong Guo, MD||Kangpu Biopharmacuticals|