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

NCT04283097 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: KPG-818-HEM-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 10

Brief Summary

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 \[SLL\]).

Conditions

Hematological Malignancies

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 4 weeks of treatment

Secondary Outcomes (15)

• PK profile of KPG-818: maximum observed plasma concentration (Cmax).

  Up to 4 weeks of treatment

• PK profile of KPG-818: time of the maximum observed plasma concentration (Tmax)

  Up to 4 weeks of treatment

• PK profile of KPG-818: area under the plasma concentration-time profile (AUC) from time zero to the last quantifiable concentration (AUC0-t).

  Up to 4 weeks of treatment

• PK profile of KPG-818: AUC from time zero extrapolated to infinity (AUC0-∞).

  Up to 4 weeks of treatment

• PK profile of KPG-818: AUC within a dosing interval (AUC0-τ).

  Up to 4 weeks of treatment

Other Outcomes (1)

• Biomarkers of KPG-818

  Up to 6 months of treatment

Study Arms (1)

Single arm

EXPERIMENTAL

KPG-818 dose escalation

Drug: KPG-818

Interventions

KPG-818 DRUG

The 4 planned dose level (cohorts) of KPG-818 will be explored: 2, 3, 4 and 5mg. Each dose of KPG-818 will be administered orally with approximately 240 ml of water daily, and used as a single agent in subjects with selected hematological malignancies (or in combination with dexamethasone weekly for MM), according to specific dosing schedule in each treatment cycle until disease progression, unacceptable toxicity, the subject withdraws, or any other study withdrawal criterion is met. The treatment of study is divided into 6 cycles.

Also known as: KPG-818 capsules

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Willing and able to provide written consent.
• Willing and able to adhere to the study visit schedule and other protocol requirements.
• Hematocytological or pathological diagnosis of MM, MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL, etc.
• Subjects who have relapsed from or are refractory to MM, MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL.
• Have measurable or assessable disease.
• Meet the laboratory requirements:
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• 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.

You may not qualify if:

• Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Currently enrolled in another clinical study, except observational studies.
• Has known active central nervous system metastases and/or lymphomatous meningitis.
• Persisting toxicities related to prior anticancer treatment \> Grade 1.
• Major surgery or significant traumatic injury within 6 weeks prior to Screening or planned major surgery during the study period.
• Received live attenuated vaccine within 4 weeks of first dose.
• Subjects with gastrointestinal disease that may significantly alter the absorption of the study drug.
• Subjects with a plasma cell leukemia.
• 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.
• Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, or pomalidomide.
• Has known or suspected hypersensitivity to the excipients contained in the formulation of investigational product (IP).
• Has been treated with an investigational agent (i.e., an agent not commercially available) within 28 days of initiating IP.
• Prior treatment of any inhibitors of PD-1 or PD-L1 within 3 months prior to initiating IP.
• Has any one of the following:
• Clinically significant abnormal ECG finding at Screening.

Sponsors & Collaborators

• Kangpu Biopharmaceuticals, Ltd.: lead

Study Sites (10)

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

BRCR Global - USA

Plantation, Florida, 33322, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Henry Ford Health System - Hemophilia and Thrombosis Treatment Center

Detroit, Michigan, 48202-2689, United States

Location

Mohamad Medical Cherry

Morristown, New Jersey, 07960, United States

Location

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

Durham, North Carolina, 27710-4000, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

UPMC CancerCenter

Pittsburgh, Pennsylvania, 15232, United States

Location

Laguna Clinical Research Associates

Laredo, Texas, 78041, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-0509, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• MD

  Kangpu Biopharmacuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: This is a open label Phase I study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation will use a standard 3+3 approach to establish a maximum tolerated dose (MTD), and the initial escalation dose level will be 2mg/day. Subjects may be enrolled at dose levels 2, 3, 4, and 5 mg and/or intermediate dosing or alternative dosing schedule

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 25, 2020
• Study Start: September 13, 2021
• Primary Completion: December 12, 2024
• Study Completion: December 12, 2024
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)