CAR-T Followed by Bispecific Antibodies | NCT04889716

NCT04889716

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Genentech, Inc.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1	Experimental	Participants 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	Drug: mosunetuzumab
Cohort 2	Experimental	Participants 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.	Drug: glofitamab Drug: obinutuzumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
mosunetuzumab	Drug	1 mg IV on Cycle 1 Day 1; 2 mg IV Cycle 1 Day 8; 60 mg IV Cycle 1 Day 15; 60 mg IV on Cycle 2 Day 1 and then 30 mg IV every 21 days beginning Cycle 2 Day 1 through Cycle 17.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Assessment of the percentage of subjects who achieve a complete metabolic response at 24 weeks from date of first infusion as measured by Cheson 14 (ie Lugano) criteria	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	24 weeks from date of first infusion of investigational agent
Assessment of the percentage of subjects who experience non-hematologic dose limiting toxicity associated with early administration of glofitimab following SOC CAR-T Cell therapy.	Non-hematologic DLTs include the following: unexpected ≥grade 3 non-hematologic that is at least possibly related to the study drug, any grade 3 event that does not improve to ≤ grade 2 within 72 hours, any grade 3 AST, ALT or total bilirubin that lasts more than 72 hours in the absence of other causes, ≥ grade 3 neurotoxicity or seizure of any grade. Cytokine Relsease Syndrome: CRS grade 4, Grade 3 CRS that does not improve to ≤ grade 2 within 72 hours. Grade 1: Temperature ≥ 38°C, no hypotension, no hypoxia. Grade 2: Temperature ≥ 38°C, hypotension not requiring vasopressors and/or hypoxia requiring low flow nasal cannula. Grade 3: Temperature ≥ 38°C, hypotension requiring a vasopressor and/or requiring high flow oxygen. Grade 4: Temperature ≥ 38°C, hypotension requiring multiple vasopressor and/or requiring positive pressure, intubation or mechanical ventilation.	63 days from the date of first infusion of glofitimab

Secondary Outcomes

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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Life expectancy of at least 12 weeks
History of relapsed or refractory large B-cell lymphoma (including transformed follicular lymphoma, and follicular lymphoma Grade 3B) who have relapsed after or failed to respond to at least one prior standard systemic treatment regimen that contains 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 +28 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 criteria 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
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
Active systemic autoimmune disease or other disease requiring chronic immunosuppressive therapy
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

Name	Role	Phone	Extension	Email
Rachel Lundberg, PA-C	Contact	215-615-5858		Rachel.Lundberg@pennmedicine.upenn.edu
Kaitlin Kennard, RN	Contact	215-615-5858		Kaitlin.Kennard@pennmedicine.upenn.edu

ID	Term
D015620	Histiocytic Disorders, Malignant
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D015614	Histiocytosis

ID	Term
C000720108	glofitamab
C543332	obinutuzumab