Inclusion Criteria:

• Men and women of age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix 13.3).
• Presence of an active hematological malignancy:
  • Part 1 (Dose Escalation): Diagnosis of B-cell DLBCL, BL/BLL, FL, MCL, HL, or LPL/WM, as documented in medical records. Enrollment of patients with other B cell malignancies may be permitted after discussion with the medical monitor;
  • Part 2 (Cohort Expansion): Diagnosis of non-GCB DLBCL, including ABC DLBCL, as documented in medical records.
• Presence of measurable disease:
  • For subjects with DLBCL, BL/BLL, FL, MCL, HL, or LPL/WM: presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures ≥1.0 cm in the  longest dimension [LD] and ≥1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed tomography [CT]);
  • For subjects with LPL/WM (Part 1), serum monoclonal immunoglobulin protein (M-protein) ≥1 g/dL (but subject does not have symptomatic hyperviscosity syndrome [HVS] and does not require plasmapheresis or other measures for control of HVS);
  • Subjects with LPL/WM are eligible for Part 1 if they fulfill criterion 4a or 4b. The presence of measurable disease and a M protein ≥1 g/dL is not necessary.
• Part 2 (Cohort Expansion): Non-GCB DLBCL histologically confirmed or confirmed by gene expression profiling, as assessed by a local laboratory (does not exclude patients that have transformed from other lymphomas that have recent histologically confirmed non-GCB DLBCL).
• Part 2 (Cohort Expansion): Subjects must have received adequate prior therapy including at a minimum including at a minimum anti-CD20 monoclonal antibody and an anthracyclinecontaining chemotherapy regimen and have failed to achieve an objective response and/or have subsequently relapsed with no available curative options.
• Part 2 (Cohort Expansion): At least one measurable lesion per revised IWG Response Criteria.
• Part 1 (Dose Escalation): Hematological malignancy has been previously treated, has relapsed after or progressed during prior therapy, and has limited potential for benefit from currently available therapy including hematopoietic stem cell transplantation.
• Determination by the investigator that the study subject is not an appropriate candidate for hematopoietic stem cell transplantation based on relevant factors (e.g., age, organ function, comorbid conditions, disease status, lack of response to preparative therapy, prior hematopoietic stem cell transplantation, or subject refusal).
• Current medical need for therapy of the hematological malignancy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or PD.
• Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥2 weeks before the start of study therapy.
• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], or neurotoxicity [Grade 1 or 2 permitted], or selected laboratory parameters [Grade 1 or Grade 2 permitted with exceptions as noted below]).
• Adequate bone marrow function:
  • Absolute neutrophil count (ANC) ≥1.0 × 109/L (Grade ≤1);
  • Platelet count ≥75 × 109/L (Grade ≤1);
  • Hemoglobin ≥8.0 g/dL (Grade ≤2) maintained for ≥2 weeks from any prior transfusion.
    • Note: In Part 2 (Cohort Expansion), Grade ≥3 neutropenia, thrombocytopenia, or anemia is permitted if abnormality is related to bone marrow involvement with hematological malignancy (as documented by bone marrow biopsy/aspirate obtained since the last prior therapy).
• Adequate hepatic function during Screening as defined below:
  • Serum ALT ≤3 x upper limit of normal (ULN) or ≤5 x ULN if liver disease is present;
  • Serum AST ≤3 x ULN or ≤5 x ULN if liver disease is present;
  • Serum bilirubin ≤1.5 x ULN (unless due to Gilbert’s syndrome or hemolysis).
• Adequate renal function:
  • Serum creatinine ≤1.5 mg/dL and /or estimated creatinine clearance (eClCR) ≥30mL/min by the Cockcroft-Gault formula [see Appendix 13.4]).
• Negative antiviral serology:
  • Negative human immunodeficiency virus (HIV) antibody;
  • Negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (PCR) testing;
  • Negative hepatitis C virus (HCV) antibody or negative HCV RNA by quantitative PCR.
• For female subjects of childbearing potential, a negative serum pregnancy test prior to start of study therapy.
• For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until ≥30 days after the final dose of study therapy.
  • Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin [βHCG]); or is menopausal (age ≥5 years with amenorrhea for ≥2 consecutive months without an alternative cause).
• For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol-recommended method of contraception from the start of study  therapy until ≥30 days after the final dose of the study therapy and to refrain from sperm donation from the start of study therapy until ≥90 days after administration of the final dose of study therapy.
  • Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
• In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject’s cancer.
• Willingness and ability to comply with scheduled visits, drug administration plan, protocol specified laboratory tests, other study procedures, and study restrictions.
• For subjects with DLBCL: Willingness to undergo a pretreatment core needle, excisional, or incisional biopsy of a lymphoma lesion; or provide archived tumor tissue for analysis.
  • Note:  Study subjects who are found after initiation of protocol therapy to have an inadequate biopsy or archival biopsy tissue will not be considered to have deviated from protocol enrollment criteria if the presence or adequacy of biopsy tissue is the only enrollment criterion that is not fulfilled.
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects, potential risks and discomforts, and other pertinent aspects of study participation.

Exclusion Criteria

• Part 2 (Cohort Expansion): history of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; adequately treated carcinoma in situ without evidence of disease; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for ≥2 years.
• Central nervous system malignancy.
  • Note: Central nervous system imaging is only required in subjects with suspected central nervous system malignancy.
• Gastrointestinal disease (e.g., gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that may interfere with drug absorption or with interpretation of gastrointestinal adverse events.
• Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 6 months prior to start of study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; unstable angina; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy; or history of congenital prolonged QT syndrome.
• Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, left bundle-branch block, 2nd-degree atrioventricular (AV) block type II, 3rd-degree AV block, Grade ≥2 bradycardia, or QTc >470 msec.
• Known symptomatic cerebral disease requiring ≥10 mg/day of prednisolone (or its equivalent). Subjects with previously diagnosed cerebral disease are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of eFT508, fulfill the steroid requirement for this disease, and are neurologically stable.
• Ongoing risk for bleeding due to active peptic ulcer disease.
• Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy.
  • Note: Subjects with localized fungal infections of skin or nails are eligible.
• Allogeneic stem cell transplantation.
• Pregnancy or breastfeeding.
• Major surgery within 4 weeks before the start of study therapy.
• Prior solid organ transplantation.
• Prior therapy with any known inhibitor of MNK1 orMNK2.
• Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids. 
  • Note: At screening, subjects may be using systemic corticosteroids (at doses of ≤10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. During study therapy, subjects may use systemic, enteric, topical or enteric corticosteroids as required for treatment-emergent conditions.
• Use of a potent inhibitor or inducer of CYP3A4 within 7 days prior to the start of study therapy or expected requirement for use of a potent CYP3A4 inhibitor or inducer during study therapy (see Appendix 13.6).
• Use of a proton pump inhibitor (e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) within 4 days prior to the start of study therapy or use of a histamine H2 blocker (e.g., cimetidine, famotidine, nizatidine, ranitidine) within 2 days prior to the start of study therapy.
• Concurrent participation in another therapeutic clinical trial.
• Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a subject’s ability to sign informed consent, adversely affect the subject’s ability to cooperate and participate in the study, or compromise the interpretation of study results.