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.

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.

This is a open label Phase I study