Inclusion Criteria:
Diagnosis (WHO 2016 criteria) of R/R B-cell NHL in dose escalation (part 1) and limited to R/R DLBCL in dose selection optimization (part 2) confirmed by biopsy and immunophenotyping
Dose escalation: at time of enrollment, R/R B-cell NHL patients per WHO 2016 criteria including DLBCL (including low grade transformed lymphoma), mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma and must:
* require treatment in the opinion of the Investigator
* received at least 2 lines of systemic therapy for B-cell NHL
Dose selection optimization: at time of enrollment, R/R DLBCL (including low grade transformed lymphoma) patients must have received 2 or 3 lines of systemic therapy for DLBCL
o Prior immunomodulatory imide drug (IMiD) therapy is allowed (e.g., lenalidomide)
Measurable disease per the 2017 International Working Group Consensus Response Evaluation Criteria for Lymphoma
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Existing archival tumor tissue (fresh frozen paraffin embedded \[FFPE\], 5 unstained slides) not older than 2 years from Cycle 1 Day 1 or willingness to provide fresh tumor biopsy during screening
Normal organ and marrow function, defined by specific laboratory parameters
Ability to take orally administered medication
Washout period prior to Cycle 1 Day 1 of SP-3164: at least 21 days or 5 half-lives (whichever is shorter) from prior systemic anticancer treatment, including chemotherapy, biologic therapy, small molecule inhibitors, monoclonal antibodies, and any investigational agents; at least 14 days from palliative radiotherapy if ≤ 10 fractions or total dose ≤ 30 gray (Gy) or at least 28 days from radiotherapy if total dose \> 30 Gy; at least 21 days from major surgery
Life expectancy of at least 3 months
Exclusion Criteria:
Patients with chronic lymphocytic leukemia, high grade B-cell lymphoma, or Richter's syndrome
Patients who have not recovered to Grade 1 toxicity or baseline due to any previous anticancer therapy according to the NCI CTCAE v5.0, excluding Grade 2 alopecia. Lymphopenia ≤ Grade 2 is allowed
Patients with primary central nervous system (CNS) lymphoma or active CNS or meningeal lymphomatous involvement
Persistent diarrhea or malabsorption of ≥ Grade 2 despite medical management
Impaired cardiac function or clinically significant cardiac disease, including symptomatic congestive heart failure, left ventricular ejection fraction (LVEF) \< 50%, unstable angina pectoris or cardiac arrhythmias, baseline QTc (Fridericia) \> 450 milliseconds, long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, myocardial infarct within 6 months of study enrollment, clinically significant pericardial disease
Solid organ transplant recipient
Allogeneic stem cell transplantation (SCT) recipient
Autologous SCT recipient \<100 days from Cycle 1 Day 1 or otherwise not fully recovered from SCT-related toxicity
Completion of CAR-T therapy \< 90 days from Cycle 1 Day 1
Systemic immunosuppressants and chronic systemic corticosteroids (at doses ≥ 10 mg/day of prednisone or equivalent) are prohibited
Malignant disease, other than that being treated in this study. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy considered indolent and that has never required therapy
Other concurrent severe or uncontrolled concomitant medical conditions that might cause unacceptable safety risks or compromise compliance with the protocol
Pregnant and breastfeeding women
Known history of HIV-positivity; known hepatitis B or hepatitis C virus infection
Men and women of child-bearing potential unwilling to use adequate contraception according to study protocol
