Clinical Trials /

CAR-T Followed by Bispecific Antibodies

NCT04889716

Description:

The research study is being conducted to test the safety and effectiveness of the experimental drug mosunetuzumab when given after CAR (genetically modified) T cells. The study is for patients who have already received a CAR T-cell infusion. Some patients who join the study will receive mosunetuzumab, other patients later in the study may receive a different experimental drug (glofitamab).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CAR-T Followed by Bispecific Antibodies
  • Official Title: Phase II Study of Dual Targeting of CD19 and CD20 Antigens Using Sequential CD19-directed 4-1BB-CD3ζ CAR-T Cells Followed by Mosunetuzumab or Glofitamab in Relapsed or Refractory Diffuse Large B-cell or Transformed Follicular Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: UPCC 48420
  • NCT ID: NCT04889716

Conditions

  • Large B-cell Lymphoma

Interventions

DrugSynonymsArms
mosunetuzumabRO7030816, BTCT4465ACohort 1
glofitamabCD20 TCBCohort 2
obinutuzumabGazyva, Gazyvaro, RO5072759, huMAb <CD20>, GA101Cohort 2

Purpose

The research study is being conducted to test the safety and effectiveness of the experimental drug mosunetuzumab when given after CAR (genetically modified) T cells. The study is for patients who have already received a CAR T-cell infusion. Some patients who join the study will receive mosunetuzumab, other patients later in the study may receive a different experimental drug (glofitamab).

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalParticipants receive mosunetuzumab 60 mg for cycles 1 and 2 (although fractionated for cycle 1), and 30 mg for all subsequent cycles after standard-of-care therapy with CD19-directed CAR T-cells
  • mosunetuzumab
Cohort 2ExperimentalParticipants receive obinutuzumab (1000 mg for each subject) and glofitamab after standard-of-care therapy with CD19-directed CAR T-cells. The dose of glofitamab for each subject will be 30 mg, other than for cycle 1, which will be 12.5 mg glofitamab fractionated over two weeks.
  • glofitamab
  • obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Life expectancy of at least 12 weeks

          -  History of relapsed or refractory DLBCL, HGBCL, PMBCL or tFL who have relapsed after
             or failed to respond to at least two prior standard systemic treatment regimens that
             include at least one prior regimen containing an anthracycline and at least one
             containing an anti-CD20-directed therapy and for whom there is no available therapy
             expected to improve survival (e.g., standard chemotherapy, autologous or allogeneic
             stem cell transplant).

          -  PET/CT scan (preferred), diagnostic CT scan, or MRI prior to CAR-T cell therapy, with
             at least one bi-dimensionally measurable lesion (≥ 1.5 cm for nodal lesion or ≥ 1cm
             for extra-nodal lesions in largest dimension by low-dose computerized tomography [CT]
             scan with FDG-uptake ≥ liver); this imaging must have been obtained within 56 days of
             receiving CAR T cell therapy.

          -  PET/CT scan (preferred), diagnostic CT scan, or MRI with at least one bi-dimensionally
             measurable lesion (≥ 1.5 cm for nodal lesion or ≥ 1cm for extra-nodal lesions in
             largest dimension by low-dose computerized tomography [CT] scan with FDG-uptake ≥
             liver); this imaging documenting measurable disease must be obtained at least day +30
             after CAR T cell infusion and prior to cycle 1 day 1.

          -  Be at least 30 days after CAR T-cell infusion at time of study enrollment.

          -  Adequate laboratory studies,

          -  Ability and willingness to take proper contraceptive precautions

        Exclusion Criteria:

          -  Had > Grade 3 cytokine release syndrome (CRS) by ASTCT criteria32 after CAR-T therapy
             or who have unresolved CRS after CAR-T therapy

          -  Had ≥ grade 2 neurologic toxicity by ASTCT criteria after CAR-T therapy or who have
             active neurologic toxicity after CAR-T therapy

          -  Treated with axicabtagene ciloleucel

          -  Inability to comply with protocol-mandated hospitalization and activities restrictions
             in the investigators' decision

          -  Pregnant or lactating, or intending to become pregnant during the study or within 3
             months after the last dose of bispecific antibody or 18 months of obinutuzumab,
             whichever comes later

          -  Prior solid organ transplantation

          -  History of autoimmune disease, including but not limited to myocarditis, pneumonitis,
             myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,
             rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with
             antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome,
             Guillain-Barré syndrome, multiple sclerosis, uveitis, vasculitis, or
             glomerulonephritis

          -  History of confirmed progressive multifocal leukoencephalopathy (PML)

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
             (or recombinant antibody-related fusion proteins)

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results Significant cardiovascular disease such as New York Heart
             Association Class III or IV cardiac disease, myocardial infarction within the last 6
             months, unstable arrhythmias, or unstable angina)

          -  Significant active pulmonary disease (e.g., bronchospasm and/or obstructive pulmonary
             disease) requiring oxygen or corticosteroid use.

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) at study enrollment, or any major
             documented infection requiring treatment with IV antibiotics or hospitalization within
             2 weeks prior to first mosunetuzumab or glofitamab administration. Empiric or
             prophylactic antibiotics administered during neutropenia or neutropenic fever without
             microbiologic evidence of infection do not exclude patients.

          -  Recent major surgery within 4 weeks prior to first mosunetuzumab or glofitamab
             administration

          -  Active or chronic infection(s) would have increased risks for toxicity if treated with
             bispecific antibody therapy, thus will be excluded.

          -  Administration of a live, attenuated vaccine within 4 weeks before first dose of study
             treatment or anticipation that such a live attenuated vaccine will be required during
             the study

          -  Received systemic immunosuppressive medications (including but not limited to
             cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
             factor agents) with the exception of corticosteroid treatment < 20 mg/day prednisone
             or equivalent within 2 weeks prior to first dose of bispecific antibody

          -  History of drug or alcohol abuse within 12 months prior to screening in the
             investigator's judgment

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's and/or Medical Monitor's judgment, precludes the patient's safe
             participation in and completion of the study, or which could affect compliance with
             the protocol or interpretation of results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of the percentage of subjects who achieve a complete metabolic response at 26 weeks from date of first infusion as measured by Cheson 14 (ie Lugano) criteria
Time Frame:26 weeks from date of first infusion of investigational agent
Safety Issue:
Description:Complete response will be assessed using Cheson 2014 or Lugano criteria, utilizing simple 5 point score (Deauville score). For this study complete response will be a score of 1 (no uptake), 2 (uptake ≤ mediastinum), or 3 (uptake >mediastinum but ≤ liver, with no new lesions, and no FDG-uptake in the bone marrow, that is not expected (i.e. due to growth factors or therapy

Secondary Outcome Measures

Measure:Determine Response Duration
Time Frame:from time of first response assessment to up to five years from last dose of bispecific antibody therapy
Safety Issue:
Description:Average length of response in months of any partial or complete metabolic responses

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

May 17, 2021