This study is a multi-center, open-label, single-arm phase I clinical study of LP-108. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL, arm A) and other B cell non-Hodgkin's lymphoma (NHL, Arm B). Each arm has a dose escalation phase (phase Ia) and expansion phase (phase Ib). During the dose escalation phase, the primary objectives are to define dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and to explore a recommended phase II dose. Dose escalation is based on the classic "3 + 3" design, while accelerated titration is applied to the initial lower doses. After the RP2Ds are determined, additional patients will be enrolled in the expansion phase to further evaluation the safety, PK and preliminary efficacy of LP-108, each therapy can enroll 12-20 subjects.

Inclusion Criteria:

• Per 2017 revised WHO lymphoma classification criteria, subject must have either:

  • (Arm A) Diagnosed with relapsed or refractory CLL and require treatment in the opinion of the Investigator.
  • (Arm B) Diagnosed with relapsed or refractory non-Hodgkin's lymphoma associated with B-cell proliferation (such as SLL \ MCL \ FL \ MZL \ DLBCL \ WM, etc.) in need of treatment.

• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1.

• Subject must have adequate bone marrow function independent of growth factor support per local laboratory reference range at Screening.

• Subject must have adequate coagulation, renal, and hepatic function, per local laboratory reference range at Screening.

• All acute toxicity from previous anti-tumor treatment or surgery has been alleviated to NCI CTCAE 5.0 ≤ Grade 1.

• All enrolled patients should take medically approved contraceptives during the entire treatment period and within 90 days after the end of treatment.

• Subjects must be willing to provide valid diagnostic evidence or accept bone marrow biopsy before treatment and accept bone marrow biopsy after treatment start.

• Patients with NHL who have undergone autologous stem cell transplantation must complete the transplantation operation for more than 6 months when enrolled, and have sufficient bone marrow function without relying on growth factor stimulation.

• Volunteer and sign informed consent, willing to follow trial protocol.

Exclusion Criteria:

• According to the 2017 revised WHO Lymphoma Classification Criteria, patients diagnosed with the following diseases: Burkitt lymphoma or Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, and post-transplant lymphoproliferative disease(PTLD) .

• Previously received other BCL-2 protein family inhibitors.

• CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL subject has undergone an allogeneic stem cell transplant.

• Subjects who have received the following treatments within 4 weeks or 5 half-lives before the first dose of LP-108:

  • Antitumor therapies including myelosuppressive chemotherapy, targeted therapy, biological therapy and / or immunotherapy;
  • Any investigational treatment;
  • Patients who have undergone major surgery, severe trauma or radiotherapy.

• Subjects who have received the following treatments within 2 weeks before the first dose of LP-108:

  • Steroids or traditional herbal medicine for antitumor purposes;
  • Strong and moderate CYP3A4/5 inhibitors and inducers, P-gp inhibitors and CYP2C8 sensitive substrates;
  • All drugs that may cause QTc interval prolongation or torsional tachycardia.

• Have had malignancies other than the indications targeted in this study in the past three years, except for basal cell carcinoma of the skin and cervical carcinoma in situ treated radically.

• Any serious and / or uncontrolled systemic disease.

• Poor cardiovascular function, in line with New York Heart Association (NYHA) cardiac function classification ≥ 2 or QTcF greater than 480ms on ≥ 3 independent ECG.

• Disease states where clinical manifestations may be difficult to control, including

  • HIV, HBV, HCV, syphilis positive or active bacterial and fungal infections;
  • Disease affects the central nervous system with obvious symptoms;
  • Autoimmune hemolytic anemia or Idiopathic thrombocytopenic purpura.

• Any gastrointestinal conditions that may severely affect the study drug absorption or pharmacokinetic parameters.

• Patients who were unable to discontinue taking CYP2C8 substrate repaglinide to control type 2 diabetes during the study.

• Subjects who cannot tolerate urine collection, venipuncture, lymph node biopsy, and bone marrow aspiration.