Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

PNT2258 will be administered at a dose of 120 mg/m2, as a 3-hour intravenous (IV) infusion on days 1-5 of a 21-day cycle. Treatment may continue (unless there is disease progression or the occurrence of unacceptable toxicity) for a total of 6 cycles of therapy.

Inclusion criteria

• Written informed consent must be obtained from the patient.
• Participants must be ≥18 years of age.
• Morphologically confirmed diagnosis of non-Hodgkin's lymphoma (NHL).
• At least a single measureable tumor mass (long axis > 1.5 cm).
• An FDG-PET positive baseline scan.

a. A positive scan is defined per revised Cheson criteria as "focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology, without a specific standardized uptake value cutoff".

• Disease that has relapsed after administration of primary therapy that included:

• Rituximab and
• CHOP, EPOCH, bendamustine or similar chemotherapy or subsequent salvage regimen.

Note: Relapse is defined as progression after a complete response to therapy or radiographic evidence of active disease after a partial response or stable disease.

• Have received three or fewer complete courses of systemic cytotoxic regimens. Note: Rituximab (alone or in combination with cytotoxic chemotherapy) is not considered a cytotoxic regimen.
• No previous exposure to PNT2258.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Have discontinued all prior anti-cancer therapies for at least 21 days; biologic therapy for at least 4 half-lives of the drug(s); radio-immunotherapy (10 weeks); autologous stem cell transplantation (SCT) (3 months) and must be at a stable baseline regarding any acute toxicity associated with prior therapy.
• Adequate organ function including:

• Hematologic Function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment. Platelets ≥ 100 x 109/L.
• Hepatic: Total Bilirubin ≤ 1.5 x ULN and serum transaminase levels ≤ 2.5 x upper limits of normal (ULN).
• Renal: Serum creatinine ≤2 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2x ULN.

Exclusion criteria

• Candidates for HDT and autologous SCT. Note: Patients who progressed > 3 months after high-dose therapy (HDT)/SCT are eligible.
• Concurrent malignancies requiring treatment.
• Symptomatic central nervous system (CNS) or leptomeningeal involvement of lymphoma.
• Concurrent serious medical conditions (as determined by the Principal Investigator) including, but not limited to, HIV-associated lymphoma; active bacterial, fungal or viral infections.
• Signs and symptoms of heart failure characterized as greater than New York Heart Association (NYHA) Class I.
• History of myocardial infarct or prolonged corrected QT (QTc) interval (>450 milliseconds (msecs) for males or >470 msecs for females) or other significant cardiac abnormalities.
• Women who are pregnant or breast-feeding.