Who can participate?

Inclusion Criteria:

• Male or female subjects, ≥ 18 years of age at the time of Screening with the following exception as outlined below:

• For T cell and B cell ALL subjects with age between 13 - 18 years, their body weight shall be ≥ 40 kg (for Phase 1b only).

•Eligible subject must have an advanced hematologic malignancy including:

Group 1:

Group 1a

Relapsed or refractory low risk tumor lysis CLL/SLL subjects (ALC < 25 x 109 /cells/L and all lymph nodes < 5 cm) who have slowly progressed on irreversible BTK inhibitors while on treatment with these agents, and received at least two prior therapies;

Group 1b

• Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;

• Morphologically confirmed diagnosis of MDS/MPN, excluding juvenile myelomonocytic leukemia (JMML), in accordance with WHO 2016 revised criteria, that is relapsed and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;

• Chronic myelomonocytic leukemia (CMML) with <9% blasts;

• Or atypical chronic myeloid leukemia (aCML) with Hgb > 10g/dL, WBC count < 50 x 109 cells/L, <10% immature circulating cells;

• Or MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) with Hgb > 10g/dL;

• Or myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC)

• CMML-2 with 10-19% blasts as defined by WHO 2016 revised criteria that is relapsed and/or refractory to prior HMA therapy;

• Relapsed and/or refractory MPN-BP as defined by WHO 2016 revised criteria that is transformed MPN with >20% myeloid blasts in the peripheral blood or bone marrow, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;

• MDS subjects with refractory anemia with excess blasts (MDS-EB; subtype MDS-EB-1 or MDS-EB-2) as defined by WHO 2016 revised criteria and/or MDS with high- or very high-risk (risk score > 4.5) per the Revised International Prognostic Scoring System (IPSS-R, refer to Appendix 11; Section 15.13) who have no available therapies known to provide clinical benefit;

• Relapsed or refractory AML subjects (including de novo AML, secondary AML evolving from MDS or MPN or other antecedent hematologic disorder, and therapy-related AML) as defined by WHO 2016 revised criteria, subjects who have no available therapies known to provide clinical benefits; subjects with prior BCL-2 inhibitor therapy are permitted. WBC needs to be ≤ 25 × 109 cells/L at the time of initiating investigational therapy (hydroxyurea is allowed to control WBC prior to and during therapy).

Group 1c

• Relapsed or refractory low risk tumor lysis NHL (NHL histologies [MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL] are to be included per the 2016 World Health Organization [WHO] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano;

• Low risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate);

• Low risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;

• Relapsed or refractory multiple myeloma (MM) subjects who have received a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 and have no treatment options available known to provide clinical benefit;

• Low risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;

Group 1d

• Relapsed or refractory ALL with dexamethasone run-in [5 days, dexamethasone 10mg/m2 (divided BID)];

• Or r/r ALL in remission but with detectable MRD (MRD +) by any detection method per institution standard of practice;

• IT chemo (per institutional SOC) is permitted prior to LP-118 C1D1 dosing, and then concomitantly on treatment if in best interest of the subject;

• Relapsed or refractory ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and/or tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and failed, or are currently ineligible/intolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and failed.

Group 2

• Relapsed or refractory intermediate and high risk tumor lysis CLL/SLL subjects who have received at least two prior therapies;

• Relapsed or refractory intermediate and high risk tumor lysis NHL (NHL histologies [MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL] are to be included per the 2016 World Health Organization [WHO] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano;

• Intermediate and high risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate);

• Intermediate and high risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;

• Intermediate and high risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;

• For Group 1d ALL subjects only, white blood cell (WBC) count ≤ 25 × 109 cells/L at the time of enrollment (glucocorticoids or hydroxyurea is permitted to control WBC count prior to and during therapy).

• Adequate cardiac function defined as shortening fraction of ≥ 40% by 2D echocardiogram without Doppler.

• Subject must have adequate bone marrow (independent of growth factor support), coagulation, renal, and hepatic function, per laboratory reference ranges at Screening as follows:

• Bone marrow criteria: Group 1 (r/r low risk tumor lysis CLL/SLL (ALC < 25 x 109 cells/L and all lymph nodes < 5 cm), NHL, RT, MM, T-PLL):

1.Absolute Neutrophil Count (ANC) ≥ 1 x 109/L (An exception is for subjects with an ANC<1 x 109/L and bone marrow heavily infiltrated with underlying disease)

2.Platelets ≥ 50 x 109/L on day of screening (entry platelet count must be independent of transfusion with 14 days of screening);

• Hemostasis criteria: Activated partial thromboplastin time (APPT) and prothrombin time (PT) ≤ 1.5 × the upper limit of normal (ULN);

• Renal function criteria: Serum creatinine ≤ ULN (per local institution reference range) or Calculated creatinine clearance (Cr Cl) ≥ 60 mL/min using 24-hour CrCl OR by Cockcroft-Gault formula using actual body weight.

• Hepatic function criteria: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × 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).

Exclusion Criteria:

• Subjects who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Subjects 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 malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with exception below

• Subject with breast cancer or prostate cancer on endocrine therapy with stable disease;

• Continuation of maintenance therapy in patients with adequately treated malignancy;

• 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.

• Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-118 treatment

• Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous therapy (excluding neuropathy):

• Any anti-neoplastic therapy including chemotherapy, hormonal therapy, radiotherapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy < 20 mg/day prednisone equivalent and hydroxyurea cytoreduction therapy according to institutional guidelines to treat disease associated symptoms are permitted);

• For MF subjects who come off JAK2 antagonists, allow washout for 2 days as these subjects progress quickly after treatment discontinuation and remain eligible (steroids may be given during these two days to allow disease control).

• Subjects in need of immediate cytoreduction should be excluded.

• Any investigational therapy.

• Live vaccines

• Subject has received the following medications, therapies or natural products within 7 days prior to the first dose of LP-118:

• Cytochrome P450, family 3, subfamily A (CYP3A) strong inhibitors (itraconazole, etc) or inducers (phenytoin, rifampin, etc);

• Inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

• There is a 28 day washout period required for subjects who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment, per discussion with the Medical Monitor.

• Subject has baseline prolongation of the heart rate-corrected QT (QTcF) interval ≥ 480 ms (calculated per Fridericia's formula [QTcF = QT/RR(1/3)]) ), a cardiovascular disability status of New York Heart Association Class ≥ 2 or associated other significant screening ECG or ultrasonic cardiogram abnormalities, per Investigator's judgement.

• Subject has significant a history of congenital long QT syndrome or Torsades de Pointes, uncontrolled or symptomatic arrhythmias, congestive heart failure, myocardial infarction, stroke or intracranial hemorrhage within 6 months prior to the first dose of LP-118.

• Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

• Uncontrolled active systemic infection (bacterial, fungal, viral);

• Known poorly controlled of human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HBsAg positive, or HBcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive);

• Unexplained fever > 38.5°C within 7 days prior to the first dose of study drug administration (at the discretion of the Investigator, if the fever is considered attributed to the subject's malignancy or an explained infection may be enrolled).

• Subjects with known and active central nervous system (CNS) involvement at Screening.