A Phase 1 Open-label, Multicenter Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of IGM-2323 in Subjects with Relapsed/Refractory Non-Hodgkin Lymphomas
Professor Chan Cheah
IGM Biosciences, Inc.
- R/R Non-Hodgkin Lymphoma
- R/R Follicular Lymphoma
- R/R Diffuse Large B-Cell Lymphoma including transformed follicular lymphoma
This trial is suitable for patients with non-hodgkins lymphoma that has returned, worsened or not responded to previous treatment. Patients will receive weekly infusions of the study drug IGM-2323 for a total of 12 weeks. IGM-2323 is a bispecific IgM antibody that eliminates cancer cells by stimulating the immune system (T-cells).
- Age ≥ 18 years.
- ECOG 0 or 1.
- Adequate bone marrow, renal, hepatic, cardiac and pulmonary function.
- Relapsed or Refractory Follicular Lymphoma (FL), and Diffuse Large B-cell Lymphoma (DLBCL), Mantle cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) in dose escalation.
- Relapsed or refractory to at least two prior systemic treatment regimens (must include anti-CD20 chemo-immunotherapy regimen).
- At least one bi-dimensionally measurable lesion (>1.5cm in it’s longest dimension by computerized tomography (CT scan).
- Not eligible for autologous stem cell transplant (DLBCL subjects), due to chemoresistant disease, medically unfit (organ function), or unwilling.
- Agree to remain abstinent or use contraception.
- Known double/triple hit lymphoma (MYC, BCL-2 and BCL-6 translocation).
- CLL, or Ricthers transformation.
- Prior allogenic stem cell transplant.
- Prior treatment with CD3 engaging bispecific antibodies.
- Impending obstruction due to lymphoma eg. superior vena cava syndrome.
- Lack of response to prior treatment with CAR-T therapy, subjects with less than 3 months from prior CAR-T therapy to first dose of IGM-2323, and prior CAR-T therapy only allowed with Medical Monitor approval.
- Prior use of any mAb within 3 weeks prior to the first dose of IGM-2323.
- Prior use of any radioimmunoconjugate or antibody drug conjugate within 4 weeks prior to first dose of IGM-2323.
- Prior treatment with systemic immunotherapeutic agents, including but not limited to cytokine therapy and anti-CTLA4, anti-PD-1, anti-PD-L1 therapeutic antibodies within 4 weeks prior to first dose of IGM-2323.
- History of severe allergic or anaphylactic reactions to mAb.
- Treatment with any chemotherapeutic agent (investigational or otherwise) within 3 weeks prior to first IGM-2323 administration.
- Treatment with any small molecule targeted therapy agent (investigational or otherwise) within 5 half-lives (or 3 weeks whichever is shorter) prior to first IGM-2323 administration.
- Treatment with radiotherapy within 1 week prior to the first IGM-2323 administration. If subjects have received radiotherapy within 4 weeks prior to the first IGM-2323 administration, subjects must have at least 1 measurable lesion outside of the radiation field.
- Current CNS lymphoma (history of CNS lymphoma allowed if in remission, no evidence of disease by head MRI and not requiring steroid therapy)
- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
- Known active clinically significant bacterial, viral (including COVID19), fungal, mycobacterial, parasitic or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to the first IGM-2323 administration.
- Known or suspected chronic active Epstein Barr Virus infection.
- Acute or chronic hepatitis C virus (HCV) infection.
- Positive serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection.
- Active autoimmune disease.
- Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide and the anti-tumor necrosis factor agents) with the exception of corticosteroid treatment ≤ 10 mg/day prednisone or equivalent within 2 weeks prior to first dose of IGM-2323.
- Presence of an abnormal electrocardiogram (ECG) or history of rhythm disorder that is clinically significant in the Investigator’s opinion, including uncontrolled atrial fibrillation/flutter or any unstable arrhythmias, second or third-degree atrioventricular (AV) heart block (AV block treated with a Pacemaker is allowed).
- Unstable angina, myocardial infarction, cardiac angioplasty or stenting within the last 6 months.
- Significant active pulmonary disease (e.g., bronchospasm and/or obstructive pulmonary disease)