CAR-T Followed by Bispecific Antibodies
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAbramson Cancer Center at Penn Medicine
About this trial
The research study is being conducted to test the safety and effectiveness of the experimental drug mosunetuzumab (Cohort 1) or obinutuzumab and glofitamab (Cohort 2) 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, in combination with obinutuzumab).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Sequential
Treatments tested in this trial
mosunetuzumab
Drug1 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.
glofitamab
Drug2.5 mg IV Cycle 1 Day 8; 10 mg IV Cycle 1 Day 15 then 30 mg every 21 days beginning Cycle 2 Day 1 through Cycle 12
obinutuzumab
Drug1000 mg IV on Cycle 1 Day 1.
Treatment groups
23 Participants
are divided into 2 treatment groupsGroup A: Cohort 1Experimental treatment 1 intervention
Group B: Cohort 2Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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
Time frame
24 weeks from date of first infusion of investigational agent2
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.
Time frame
63 days from the date of first infusion of glofitimabSecondary outcomes
1
Determine Response Duration
Average length of response in months of any partial or complete metabolic responses
Time frame
from time of first response assessment to up to five years from last dose of bispecific antibody therapySponsors and contacts
Click on the lead sponsor to view all of their trials.
Abramson Cancer Center at Penn Medicine
Lead sponsor
Genentech, Inc.
Collaborator
Source ClinicalTrials.gov