Inclusion Criteria:
A subject will be eligible for study participation if he/she meets the following criteria:
* Subjects are eligible with B-cell malignancies, WM, FL, MCL, MZL, DLBCL, HCL, CLL, SLL, based upon 2016 updated WHO classification. Those subjects with WM, FL, MCL, DLBCL, or HCL must have received at least 2 prior systemic therapies.
* Low-grade B-cell lymphomas as follicular Grade 1, 2, or 3A, marginal zone or small lymphocytic lymphoma.
* Subject must have adequate coagulation, renal, and hepatic function, per local laboratory reference ranges at Screening as follows:
* Activated partial thromboplastin time (APTT) and prothrombin time (PT) not to exceed 1.5 × ULN
* Calculated creatinine clearance (CrCl) ≥ 60 mL/min using 24-hour CrCl OR Cockcroft-Gault formula.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 ×ULN; Bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a bilirubin \> 1.5 × ULN, per discussion between the Investigator and the Medical Monitor).
* Subjects must have adequate bone marrow independent of growth factor support per local laboratory reference range at screening as follows:
* Absolute Neutrophil Count (ANC) ≥1000/uL;
* An exception is for subjects with an ANC\<1000/uL and bone marrow heavily infiltrated with underlying disease (approximately 60% or more) may use growth factor to achieve the ANC eligibility criteria per discussion between the Investigator and the Medical Monitor.
* Platelet count ≥ 50,000/µL - OR - Platelet count ≥ 20,000/ µL if thrombocytopenia is clearly due to CLL disease under study (per Investigator discretion)
* Hemoglobin ≥8.0g/dL, and can be achieved by transfusion
Exclusion Criteria:
A subject will not be eligible for study participation if he/she meets any of the following criteria.
* Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug, or has not recovered to ≤ Grade 1 clinically significant adverse effect(s)/toxicity(s) of the previous therapy (other than alopecia):
* Any anti-cancer therapy including chemotherapy, biologic or immunotherapy, radiotherapy, etc;
* Any investigational therapy, including targeted small molecule agents.
* For CLL subjects who come off BCR antagonists (BTK inhibitors, PI3K inhibitors, etc.) treatment, allow washout for 2 days as these subjects progress quickly after treatment discontinuation and then remain eligible (steroids may be given during these two days to allow disease control).
* Subjects who require immediate cytoreduction. However, subjects may receive up to two days of steroids for symptoms of impending organ impairment and remain eligible.
* Subject has received the following medications or therapies within 7 days prior to the first dose of study drug:
* Steroid therapy (at dosages equivalent to prednisone \>20 mg/day) for anti-neoplastic intent (except as noted in exclusion criteria #3);
* Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors and strong CYP2C8 inducers/inhibitors.
* Potent CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.
* Subjects require treatment with systemic acid-reducing agents including H-2-receptor antagonists and proton pump inhibitors with the following exceptions:
* Proton pump inhibitors should be discontinued at least 7 days prior and held throughout the study
* If concurrent use of an H2 blocking agent is necessary, it must be administered only between 2 and 3 hours after the dose of LP-168. If not taken during this time, the dose of H2 blocking agents should not be taken again until 2-3 hours after the next dose of LP-168.
* If concurrent use of a local antacid is necessary, it must be administered 2 or more hours before and/or 2 or more hours after the dose of LP-168.
* Subject has significant screening electrocardiogram (ECG) abnormalities including. 2nd degree AV block type II 3rd degree block, Grade 2 or higher bradycardia, and corrected QT interval (QTc) ≥ 480ms.
* Serum amylase \> 1.5 × ULN or serum lipase \> 1.5 × ULN.
* Subject has any history of Richter's transformation for Phase 1a portion of the trial.
* Subjects who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 90 days of the first dose of LP-168, or patients on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Patients in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is permitted.
* Subject has a history of other active malignancies other than B-cell malignancies within the past 3 years prior to study entry, with the exception of:
* Adequately treated in situ carcinoma of the cervix uteri;
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
* Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
* Subject requires anticoagulation with Warfarin.
