Safety, Tolerability and Pharmacokinetics Study of KPG-818 in Hematological Malignancies Subjects

Kangpu Biopharmaceuticals, Ltd.30 enrolled

Overview

This is 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. Approximately 30 patients will be enrolled for dose escalation of 4 dose levels. Indication: Hematological malignancies (multiple myeloma \[MM\], mantle cell lymphoma \[MCL\], diffuse large B-cell lymphoma \[DLBCL\], adult T-cell leukemia-lymphoma \[ATL\], and indolent non Hodgkin lymphomas such as follicular lymphoma \[FL\] and chronic lymphocytic leukemia \[CLL\]/small lymphocytic lymphoma \[SLL\]).

This will be a dose escalation study in subjects with selected hematological malignancies. KPG-818 will be used in combination with dexamethasone in subjects with MM, and as monotherapy for other selected hematological malignancies. Each dose of KPG-818 will be administered orally until the completion of treatment cycles, or progressive disease (PD), unacceptable toxicity, the subject withdraws, or any other study withdrawal criterion is met. The highest dose level which may be tested is 5 mg KPG-818 and dose levels 2, 3, 4, and 5 mg and/or intermediate dosing or alternative dosing schedule may be explored. Each dose level (1-4) will be tested using the standard 3+3 design. DLT will be assessed during the DLT evaluation period (Cycle 1) and the treatment of study is divided into 6 cycles.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hematological Malignancies

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. ≥ 18 years of age 2. Willing and able to provide written consent. 3. Willing and able to adhere to the study visit schedule and other protocol requirements. 4. Hematocytological or pathological diagnosis of MM, MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL, etc. 5. Subjects who have relapsed from or are refractory to MM, MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL. 6. Have measurable or assessable disease. 7. Meet the laboratory requirements: 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 9. Males and females of childbearing potential must agree to use at least two methods of contraception and continue until 3 months after the completion of study treatment. Exclusion Criteria: 1. Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Currently enrolled in another clinical study, except observational studies. 3. Has known active central nervous system metastases and/or lymphomatous meningitis. 4. Persisting toxicities related to prior anticancer treatment \> Grade 1. 5. Major surgery or significant traumatic injury within 6 weeks prior to Screening or planned major surgery during the study period. 6. Received live attenuated vaccine within 4 weeks of first dose. 7. Subjects with gastrointestinal disease that may significantly alter the absorption of the study drug. 8. Subjects with a plasma cell leukemia. 9. Subjects with prior history of malignancies, other than MM, lymphoma, or CLL/SLL, unless the subject has been free of the disease for ≥ 5 years. 10. Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, or pomalidomide. 11. Has known or suspected hypersensitivity to the excipients contained in the formulation of investigational product (IP). 12. Has been treated with an investigational agent (i.e., an agent not commercially available) within 28 days of initiating IP. 13. Prior treatment of any inhibitors of PD-1 or PD-L1 within 3 months prior to initiating IP. 14. Has any one of the following: * Clinically significant abnormal ECG finding at Screening. * Congestive heart failure. * Myocardial infarction within 12 months prior to initiating IP. * Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris. * Peripheral neuropathy ≥ Grade 2. * Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St. John's Wort or related products within 2 weeks prior to dosing and during the course of study. 15. Has current or prior use of immunosuppressive medication within 14 days prior initiating IP. 16. Subject known to test positive for human immunodeficiency virus, active hepatitis B, or active hepatitis C. 17. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis. 18. Subject is a female who is pregnant, nursing, or breastfeeding.

Locations (10)

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

BRCR Global - USA

Plantation, Florida, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Henry Ford Health System - Hemophilia and Thrombosis Treatment Center

Detroit, Michigan, United States

Mohamad Medical Cherry

Morristown, New Jersey, United States

Duke University Health System - Duke Endoscopy - Duke Clinic 2H

Durham, North Carolina, United States

Providence Portland Medical Center

Portland, Oregon, United States

UPMC CancerCenter

Pittsburgh, Pennsylvania, United States

Laguna Clinical Research Associates

Laredo, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Outcomes

Primary Outcomes

Treatment-Emergent Adverse Events [Safety and Tolerability]

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.

Time frame: Up to 6 months of treatment

Recommended Phase 2 Dose (RP2D)

Maximum tolerated dose defined as the highest dose level at which 33% or less subjects experience DLT as defined by the protocol.