PSB202 in Patients With Previously Treated-, Relapsed-, Indolent B-Cell Malignancies

Inclusion Criteria

• •Phase 1a (dose escalation):
• •1. Histologically confirmed CD20+ expressing indolent NHL (defined below), CLL or WM, failed or intolerant to standard of care therapies;
• •2. Relapsed/refractory following at least 2 prior lines of standard of care treatment. Prior treatments received must be documented on the enrollment request form. For FL, prior treatment must have included at least 1 rituximab containing regimen.
• •3. First three dose levels: in the opinion of the investigator, able to tolerate potentially subtherapeutic doses of PSB202 for the duration of a 28-day DLT observation window.
• •Phase 1b - Dose Expansion:
• •4. Histologically confirmed CD20+ expression. For CD37+, if unavailable from the chart at screening, CD37+ expression may be documented from a new or archived blood specimen after enrollment.
• •5. Relapsed indolent NHL: histologies that may be included are CLL/SLL, MZL, MALT-lymphoma, follicular NHL, MCL or WM failed, relapsed/refractory or intolerant to at least 2 standard of care therapies. (APPENDIX B). For FL, prior treatment must have included rituximab. MCL must have received a prior alkylating agent.
• •6. Patients must have documented disease progression after at least two prior standard-of-care regimens.
• •7. Patients must have measurable disease.
• •All Patients:
• •8. Signed Informed Consent;
• •9. Eastern Cooperative Oncology Group (ECOG) 0-2
• •10. Last dose of any anti-CD20 antibody therapy must have been \>4 weeks before the first dose of PSB202
• •11. Patients with a medical history of Covid-19 positivity at within 6 months prior to enrollment, must be retested within 7 days of enrollment and confirm Covid-19 negativity by a PCR-test.
• •12. At least 18 years of age. There is no upper age restriction.
• •13. Four weeks wash-out from any other prior cancer therapy, including rituximab or BTK-inhibitors. However, some heavily pretreated patients are at risk for significant morbidity from accelerated disease progression or "flare" when treatment is discontinued prior to the initiation of subsequent effective therapy. Absent residual toxicity and with documented Medical Monitor approval, such patients may receive study drug after five drug half-lives have passed following discontinuation of the immediate pre-study therapy.
• •14. Adequate hematologic and coagulation status, defined as the following on C1D1 before treatment:
• •1. Absolute neutrophil count (ANC) ≥ 0.75 billion/L; not requiring growth factors; after the DLT period, growth factor support is allowed and considered supportive care.
• •2. Platelet count ≥75 billion/L not requiring transfusion support; if there is documented bone marrow involvement, platelet transfusions may be used up to 7 days prior to C1D1 to achieve this threshold.
• •3. Hemoglobin (Hb) ≥9 mg/dL not requiring transfusion support or growth factors. After the DLT period, growth factor support is allowed and considered supportive care.
• •4. Adequate coagulation, defined as aPTT and PT (INR) not greater than 1.5 × upper limit of normal (ULN) (patients appropriately anticoagulated for a preexisting medical condition \[e.g., atrial fibrillation\] may be eligible with documented Sponsor approval).
• •15. Adequate hepatic function, defined as:
• •1. ALT or AST ≤2.5 X the ULN or ≤5 X ULN with documented liver involvement.
• •2. Total bilirubin ≤1.5 X ULN or ≤3 X ULN with documented liver involvement and/or Gilbert's Disease
• •3. Adequate renal function, with estimated glomerular filtration rate (eGFR) ≥50 mL/minute.
• •16. Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
• •17. Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment; this may include barrier methods such as condom or diaphragm with spermicidal gel.
• •29. Active auto-immune cytopenia (e.g., autoimmune hemolytic anemia \[AIHA\], idiopathic thrombocytopenic purpura \[ITP\])
• •30. Cerebrovascular accident (CVA), Transient ischemic attack (TIA), myocardial infarction, unstable angina, or New York Heart Association (NYHA) class III or IV heart failure \< 6 months of study screening; mean ECG QT-interval corrected according to Fridericia's formula (QTcF) \> 450 milliseconds (ms) (males) or \> 470 ms (females) obtained from three ECGs; uncontrolled arrhythmia \< 3 months of study screening. Patients with rate-controlled arrhythmias may be eligible for study entry at discretion of the Investigator.
• •31. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
• •32. Tested positive for Human Immunodeficiency Virus (HIV) is excluded (due to potential drug-drug interactions between anti-retroviral medications and PSB202 and risk of opportunistic infections). For patients with unknown HIV status, HIV testing will be performed at Screening
• •33. Active viral hepatitis (B or C, HBsAg, anti-HBs/HBcAb and anti-HCV Ab tests) as demonstrated by positive serology or requiring treatment. Subjects who are anti-HBs/HBcAb (+) without detectable HBV-DNA are eligible. Subjects with a history of Hepatitis C and have received successful curative treatment are eligible.
• •34. Pregnancy or lactation.
• •35. Active autoimmune disease or history of autoimmune disease requiring systemic therapy \< 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease, Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that has not been active in the 2 years prior to study screening are eligible.
• •36. History of drug-induced liver injury or cirrhosis
• •37. History of pneumonitis or interstitial lung disease
• •38. Patients with significant medical diseases or conditions, as assessed by the Investigator and Sponsor, that would substantially increase the risk-benefit ratio of participating in the study.
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