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

NCT05003141 | Unknown Phase 1 FDA Drug

• 1 other identifier: PSB202-01
• Study Type: interventional
• Target: 110
• Locations: 3 countries
• Sites: 5

Brief Summary

Product: PSB202 is a novel biological entity consisting of two engineered monoclonal antibodies, an Fc-enhanced humanized type II anti-CD20 IgG1 (PSB102) and a humanized anti-CD37 IgG1 (PSB107), that target B-cells. PSB202 is manufactured to work as a single product with the two components of PSB202 enabling a distinct dual target-specific antibody directed cell killing of B-cells. Study: Multi-center-, International Phase 1a/1b (Escalation/Expansion) study in patients with indolent-, relapsed-, B-cell malignancies. The Phase 1a (Dose Escalation) part of study follows a 3+3 design.

Conditions

Follicular Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Indolent Lymphoma; Refractory B-Cell Lymphoma; MALT Lymphoma

Keywords

Phase 1; CD20+; CD37+; B-cell malignancy; B-cell lymphoma; monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Adverse Events, defined and graded per NCI Common Toxicity criteria (V5)

  Through study completion; up to 27 weeks

• Dose Limiting Toxicity (DLT)

  Defined Grade 3, Grade 4, and Grade 5 events occurring during the DLT-observation period

  3 weeks

Secondary Outcomes (4)

• Peak Plasma Concentration (Cmax)

  2 months

• Area under the Plasma Concentration versus Time Curve (AUC)

  2 months

• Number of Patients with measurable Anti-Lymphoma Response

  Up to 27 weeks

• Change in CD20+ cell counts

  2 months

Study Arms (1)

Single-arm, escalating dose levels

EXPERIMENTAL

3 + 3 Phase 1 dose escalation design; sequential ascending dose levels.

Drug: PSB202

Interventions

PSB202 DRUG

PSB202 is an antibody combination product comprised of two full-length monoclonal antibodies, PSB102 and PSB 107, respectively targeting CD20 and CD37. PSB202 is manufactured to work as a single product.

Single-arm, escalating dose levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1a (dose escalation):
• Histologically confirmed CD20+ expressing indolent NHL (defined below), CLL or WM, failed or intolerant to standard of care therapies;
• 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.
• 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:
• 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.
• 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.
• Patients must have documented disease progression after at least two prior standard-of-care regimens.
• Patients must have measurable disease.
• All Patients:
• Signed Informed Consent;
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Last dose of any anti-CD20 antibody therapy must have been \>4 weeks before the first dose of PSB202
• 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.
• At least 18 years of age. There is no upper age restriction.

You may not qualify if:

• Phase 1a (dose escalation) only:
• NHL with bulky disease defined as a mass ≥10 cm in longest diameter
• Transformation (e.g., Richter's transformation, prolymphocytic leukemia, transformed NHL, blastoid lymphoma) prior to planned start of PSB202. In addition, no concurrent investigational therapy is permitted.
• All patients: Phase 1a (dose escalation) and Phase 1b (dose expansion):
• Major surgery within 4 weeks prior to planned start of PSB202
• Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment, except for patients receiving radiation to more than 30% of the bone marrow or receiving whole brain radiotherapy, which must be completed at least 4 weeks prior to the first dose of study treatment
• Continuation of certain standard of care anticancer therapies, including hormonal therapy for breast and prostate cancer, and growth factor support after completion of the DLT-period, is allowed.
• Therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose of PSB202. PSB202 may be started sooner after prior investigational agent or anticancer therapy if considered by the Investigator to be safe and within the best interest of the patient (e.g., to avoid disease flare) and with documented Sponsor approval.
• Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 or greater at the time of starting study treatment except for alopecia.
• History of autologous stem cell transplant (auto-SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within the past 180 days with any of the following: cytopenias from incomplete blood cell count recovery post-transplant, need for anti-cytokine therapy, residual symptoms of neurotoxicity \> Grade 1, or ongoing immunosuppressive therapy.
• Active graft versus host disease (GVHD, including resultant from any prior solid organ transplants, if received), or ongoing immunosuppressive therapy.
• History of allogeneic stem cell transplant (allo-SCT) or allogeneic CAR-T at any time in the patient's medical history
• Known central nervous system (CNS) involvement by lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of active CNS-disease may be eligible if a clinical rationale is provided by the Investigator and with documented Sponsor approval
• Active auto-immune cytopenia (e.g., autoimmune hemolytic anemia \[AIHA\], idiopathic thrombocytopenic purpura \[ITP\])
• 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.

Sponsors & Collaborators

• Qilu Puget Sound Biotherapeutics (dba Sound Biologics): lead

Study Sites (5)

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

Epworth Healthcare

East Melbourne, Victoria, 3002, Australia

RECRUITING

One Clinical research

Perth, Western Australia, 6153, Australia

RECRUITING

Ruijin Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• Lindsey E. Roeker, MD

  Memorial Sloan-Kettering Cancer Center, New York, NY

  STUDY CHAIR

Central Study Contacts

Jelle W. Kijlstra, MD

CONTACT

2069091125; jelle@soundbiologics.com

Joan Sun

CONTACT

8622132588; joan.sun@qilu-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1a: 3+3 dose escalation design Phase 1b: 3 Expansion cohorts (N=20 each). Expansion beyond N=20 in a cohort is predicated on an ORR of at least 35% (Futility threshold) observed in the initial N=20 in the cohort.

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: August 12, 2021
• Study Start: November 15, 2021
• Primary Completion: July 1, 2023
• Study Completion: January 1, 2024
• Last Updated: March 28, 2022

Record last verified: 2022-03

Locations

US (2); AU (2); CN (1)