Inclusion Criteria

Subjects must satisfy all of the following criteria at the Screening visit unless otherwise stated:

1. ≥ 18 years of age at the time of signing the informed consent form (ICF).
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 ALL FDA approved therapies* known to provide clinical benefit for the specific disease, unless the subject is not eligible for the approved therapy. *Definition of ALL FDA approved therapies are specified as below: Prior treatments for MM subjects:
   • Received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and an anti-CD38 antibody (induction with or without a bone marrow transplant with or without maintenance therapy is considered one regimen).
   • Refractory disease defined as disease that is nonresponsive to therapy (failure to achieve minimal response or development of progressive disease) or disease progression within 60 days from the last dose of their last myeloma therapy.
   Prior treatments for NHL subjects:
   • ATL: at least 2 prior lines of therapy containing alkylator-based chemotherapy.
   • MCL: at least 2 prior lines of therapy, including CD20 antibody and alkylator chemotherapy, and a Bruton's tyrosine kinase (BTK) inhibitor.
   • DLBCL: at least 2 prior lines of therapy, including prior CD20 antibody therapy, and has received prior autologous bone marrow transplant (or is ineligible for bone marrow transplant).
   • FL: at least 2 prior lines of therapy, including CD20 antibody therapy and alkylator chemotherapy.
   • CLL/SLL: at least 2 prior lines of therapy for CLL/SLL and require treatment by 2018 iwCLL criteria.
   • Other indolent NHL: Subjects must have been treated with all standard of care therapies available to the subject which, in the assessment of the investigator, may be beneficial to the subject.
6. Have measurable or assessable disease. For MM:
   • M-protein quantities ≥ 0.5 g/dL by serum protein electrophoresis (SPEP or SIFE) or
   • M-protein quantities ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (UPEP or UIFE) or
   • Serum free light chain (FLC) levels > 100 mg/L involved light chain and an abnormal kappa/lambda (κ/λ) ratio in subjects without detectable serum or urine M-protein or
   • For subjects with immunoglobulin (Ig) class A (IgA) myeloma whose disease can only be reliably measured by quantitative Ig measurement, a serum IgA level ≥ 0.50 g/dL.
   For MCL, DLBCL, ATL, indolent lymphoma, such as FL and CLL/SLL, etc.: • At least 1 bidimensionally measurable lesion larger than 1.5 cm in largest dimension by computed tomography (CT), positron emission tomography CT (PET-CT), or magnetic resonance imaging (MRI) scan.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. ECOG of 2 is allowed during dose expansion.
8. Males and females of childbearing potential must agree to use at least two methods of contraception, as detailed in Section 6.1.3, during the study treatment and continue until 3 months after the completion of study treatment.

Exclusion Criteria

Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated:

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 according to NCI CTCAE v5.0.
5. Major surgery or significant traumatic injury within 6 weeks prior to Screening or planned major surgery during the study period.
6. Any of the following laboratory abnormalities:
   • Absolute neutrophil count (ANC) < 1.0 × 109/L.
   • Hemoglobin ≤ 7.5 g/dL (red blood cell [RBC] transfusion is allowed to meet eligibility).
   • Platelet count ≤ 75 000/μL (except in the case of bone marrow involvement when platelet count must not be < 50 000/μL).
   • Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L).
   • AST and/or ALT ≥ 2.5 × ULN or ≥ 5.0 × ULN if liver tumor is present.
   • Total bilirubin > 1.5 × ULN.
   • Estimated serum creatinine clearance of ≤ 60 mL/min or requiring dialysis；estimated serum creatinine clearance between 50-60 mL/min may be enrolled for KPG-818 dose ≤ 10mg/day. For subjects with serum creatinine clearance between 50-60 mL/min at screening, serum creatinine clearance levels should be monitored during the study.
7. Subjects with gastrointestinal disease that may significantly alter the absorption of the study drug.
8. Subjects with a prior history of malignancies, other than MM, lymphoma, or CLL/SLL, unless the subject has been free of the disease for ≥ 5 years with the exception of the following noninvasive malignancies:
   • Basal cell carcinoma of the skin.
   • Squamous cell carcinoma of the skin.
   • Carcinoma in situ.
   • Incidental histological findings of prostate cancer such as T1a or T1b using the tumor/node/metastasis classification of malignant tumors or prostate cancer that is curative.
9. Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, or pomalidomide.
10. Has known or suspected hypersensitivity to the excipients contained in the formulation of investigational product (IP).
11. Has received any of the following within the last 14 days of initiating IP:
    • Plasmapheresis
    • Radiation therapy other than local therapy for MM associated bone lesions
    • Use of any systemic myeloma/lymphoma/CLL/SLL drug therapy.
12. Has been treated with an investigational agent (i.e., an agent not commercially available) within 28 days or 5 half-lives (whichever is longer) 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, including QTcF interval elongation (> 480 ms), at Screening.
    • Congestive heart failure (New York Heart Association Class III or IV).
    • 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. The following are exceptions to this criterion:
    • Intranasal, inhaled, topical, or local steroid injections (e.g., intra-articular injection)
    • Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
16. Subject known to test positive for human immunodeficiency virus, active hepatitis B, or active hepatitis C. Note: subjects who are hepatitis B core antibody (anti-HBc) positive and hepatitis B surface antigen (HBsAg) negative are required to have a negative hepatitis B DNA PCR result before randomization and must be willing to undergo the DNA PCR testing during the study. Subjects who are HBsAg positive or hepatitis B DNA PCR positive will be excluded. Subjects who are hepatitis C virus antibody positive are required to have a negative hepatitis C RNA PCR result. Subjects who are hepatitis C RNA PCR-positive will be excluded.
17. Subjects with any active or uncontrolled infection.
18. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis.
19. Subject is a female who is pregnant, nursing, or breastfeeding.