A Phase I Study of LP-108 in Patients With Relapsed or Refractory B-cell Lymphoma

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 theopinion of the Investigator.
• (Arm B) Diagnosed with relapsed or refractory non-Hodgkin's lymphoma associatedwith B-cell proliferation (such as SLL \ MCL \ FL \ MZL \ DLBCL \ WM, etc.) inneed of treatment.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less thanor equal to 1.
• Subject must have adequate bone marrow function independent of growth factor supportper local laboratory reference range at Screening.
• Subject must have adequate coagulation, renal, and hepatic function, per locallaboratory reference range at Screening.
• All acute toxicity from previous anti-tumor treatment or surgery has been alleviatedto NCI CTCAE 5.0 ≤ Grade 1.
• All enrolled patients should take medically approved contraceptives during the entiretreatment period and within 90 days after the end of treatment.
• Subjects must be willing to provide valid diagnostic evidence or accept bone marrowbiopsy before treatment and accept bone marrow biopsy after treatment start.
• Patients with NHL who have undergone autologous stem cell transplantation mustcomplete the transplantation operation for more than 6 months when enrolled, and havesufficient 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 diagnosedwith the following diseases: Burkitt lymphoma or Burkitt-like lymphoma, lymphoblasticlymphoma/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 NHLsubject has undergone an allogeneic stem cell transplant.
• Subjects who have received the following treatments within 4 weeks or 5 half-livesbefore 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 firstdose of LP-108:
• Steroids or traditional herbal medicine for antitumor purposes;
• Strong and moderate CYP3A4/5 inhibitors and inducers, P-gp inhibitors and CYP2C8sensitive 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 pastthree years, except for basal cell carcinoma of the skin and cervical carcinoma insitu treated radically.
• Any serious and / or uncontrolled systemic disease.
• Poor cardiovascular function, in line with New York Heart Association (NYHA) cardiacfunction 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 orpharmacokinetic parameters.
• Patients who were unable to discontinue taking CYP2C8 substrate repaglinide to controltype 2 diabetes during the study.
• Subjects who cannot tolerate urine collection, venipuncture, lymph node biopsy, andbone marrow aspiration.