Relapsed/Refractory Large B-cell Lymphoma
Conditions
Keywords
Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), GM-CSF antibody, Chimeric Antigen Receptor (CAR), CD19
Brief summary
The primary objectives of this study are: Phase 1: To evaluate the safety of sequenced therapy with lenzilumab and axicabtagene ciloleucel in participants with relapsed or refractory large B-cell lymphoma and identify the most appropriate dose of lenzilumab for Phase 2. Phase 2: To evaluate the incidence of neurologic events with sequenced therapy given at the recommended Phase 2 dose (RP2D) of lenzilumab in participants with relapsed or refractory large B-cell lymphoma.
Detailed description
This study was intended to be a Phase 1/2, but the planned Phase 2 part has been canceled. All participants who received an infusion of lenzilumab and axicabtagene ciloleucel will be provided the opportunity to transition to a separate long-term follow-up (LTFU) study, KT-US-982-5968.
Interventions
DRUGFludarabine
Administered according to package insert
BIOLOGICALLenzilumab
Administered as an IV infusion
BIOLOGICALAxicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously.
DRUGCyclophosphamide
Administered according to package insert
Sponsors
Humanigen, Inc.
Kite, A Gilead Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Individuals with large B-cell lymphoma, including Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, Primary mediastinal large B-cell lymphoma (PMBCL), High-grade B-cell lymphoma (HGBL), and DLBCL arising from Follicular lymphoma (FL) * Individuals must have relapsed disease after 2 or more lines of systemic therapy, or chemorefractory disease defined as the following: * No response to first-line therapy, including the following: * Progressive disease (PD) as best response to first therapy * Stable disease (SD) as best response after ≥ 4 cycles of first-line therapy (eg, 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP)), with SD duration no longer than 6 months from the last dose of therapy * No response to ≥ 2 lines of therapy, including the following: * PD as best response to most recent therapy * SD as best response after ≥ 2 cycles of last line of therapy * Individuals must have received adequate prior therapy including at a minimum: * Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and * An anthracycline-containing chemotherapy regimen * At least 1 measurable lesion according to the International Working Group Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. * Magnetic resonance imaging of the brain showing no evidence of central nervous system (CNS) lymphoma * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Individuals with a known medical history of tuberculosis or a risk for tuberculosis exposure require negative tuberculosis testing by either tuberculin skin test or interferon gamma release assay. * Adequate bone marrow function as evidenced by: * Absolute neutrophil count ≥ 1000/μL * Platelets ≥ 75,000/μL * Absolute lymphocyte count ≥ 100/μL * Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by: * Creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min * Serum alanine aminotransferase or aspartate aminotransferase ≤ 2.5 upper limit of normal * Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's Syndrome * Cardiac ejection fraction ≥ 50% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings * No clinically significant pleural effusion * Baseline oxygen saturation \> 92% on room air Key
Exclusion criteria
* History of Richter's transformation of chronic lymphocytic leukemia * Autologous stem cell transplant (SCT) within 6 weeks of planned axicabtagene ciloleucel infusion * History of allogeneic stem cell transplantation * Prior CD19 targeted therapy or prior CAR T cell therapy * History of pulmonary alveolar proteinosis (PAP) * History of severe, immediate hypersensitivity reaction attributed to aminoglycosides * Known history of human immunodeficiency virus (HIV) infection, hepatitis B (HBsAg positive) or hepatitis C (HCV) (anti-HCV positive) infection. A history of hepatitis B or hepatitis C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing. * Individuals with detectable Cerebrospinal fluid (CSF) malignant cells, or brain metastases, or with a history of CNS lymphoma, CSF malignant cells or brain metastases * History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene | First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days. | A DLT was defined as the following sequenced therapy-related events with onset within the first 28 days following lenzilumab and axicabtagene ciloleucel infusions: * Grade 4 neutropenia lasting longer than 21 days from the day of cell transfer * Grade 4 thrombocytopenia lasting longer than 28 days from the day of cell transfer * Any sequenced therapy-related AE requiring intubation, including Grade 4 encephalopathy requiring intubation for airway protection * Any sequenced therapy-related Grade 5 event |
| Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration | Up to 28 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome | Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first. | — |
| Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events | Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first. | — |
| Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators | First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months). | CR rate: percentage of participants with CR (CMR;CRR). CMR: positron emission tomography(PET)5-point scale(5PS) scores of 1(no uptake above background), 2(uptake ≤ mediastinum), 3(uptake \> mediastinum but ≤ liver) with/without a residual mass); no new sites; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter (LDi) of a lesion; no extra lymphatic sites; absent non-measured lesion;organ enlargement regress to normal; no new sites; and bone marrow normal by morphology. |
| Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators | First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months). | ORR: Percentage of participants with CR(CMR;CRR) or PR(partial metabolic response(PMR);partial radiologic response (PRR)).CMR:PET 5PS scores of 1,2,3 with/without a residual mass;no new sites;no evidence of FDG-avid disease in bone marrow.CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in LDi of a lesion;no extra lymphatic sites;absent non-measured lesion;organ enlargement regress to normal;no new sites;bone marrow normal by morphology.PMR:5PS scores of 4(uptake moderately higher than liver),or 5(uptake markedly higher than liver and/or new lesions),with reduced uptake compared to baseline and residual masses of any size;no new sites;residual update \> update in normal bone marrow but reduced compared with baseline.PRR:≥ 50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites;absent/normal, regressed, but no increase of nonmeasured lesions;spleen regressed by \> 50% in length beyond normal;no new sites. |
| Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events | Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. | — |
| Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators | First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months). | PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause. |
| Phase 1 and Phase 2: Overall Survival (OS) | First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months). | OS is defined as the time from axicabtagene ciloleucel infusion to the date of death. |
| Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | Baseline up to Week 4 | Peak is defined as the maximum post-baseline level of the analyte from baseline to Week 4. |
| Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood | Baseline up to Month 3 | Peak is defined as the maximum number of CAR T cells in blood measured after the axicabtagene ciloleucel infusion. |
| Phase 1 and Phase 2: Duration of Response (DOR) in Participants Who Experience an Objective Response Per IWG Lugano Classification as Determined by Study Investigators | First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months). | DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause. Objective response is defined in outcome measure (OM) 7. |
| Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events | Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States.
Pre-assignment details
9 participants were screened. The study was terminated earlier than planned, and thus the study did not proceed to Phase 2.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1/Cohort 1 Participants received 500 mg/m\^2 cyclophosphamide intravenously (IV) and 30 mg/m\^2/day fludarabine IV lymphodepleting chemotherapy followed by sequenced therapy of 600 mg lenzilumab IV and axicabtagene ciloleucel IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0 to determine a recommended Phase 2 dose (RP2D) of lenzilumab. For participants weighing greater than 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells was administered. | 3 |
| Phase 1/Cohort 2 Participants received 500 mg/m\^2 cyclophosphamide IV and 30 mg/m\^2/day fludarabine IV lymphodepleting chemotherapy followed by sequenced therapy of 1800 mg lenzilumab IV and axicabtagene ciloleucel IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0 to determine RP2D of lenzilumab. For participants weighing greater than 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells was administered. | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 2 |
| Overall Study | Rolled over to long-term follow-up study after study terminated | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Phase 1/Cohort 1 | Phase 1/Cohort 2 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 2 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 12 | 62 years STANDARD_DEVIATION 15.7 | 65 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 | 3 / 3 |
Outcome results
Primary
Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene
A DLT was defined as the following sequenced therapy-related events with onset within the first 28 days following lenzilumab and axicabtagene ciloleucel infusions: * Grade 4 neutropenia lasting longer than 21 days from the day of cell transfer * Grade 4 thrombocytopenia lasting longer than 28 days from the day of cell transfer * Any sequenced therapy-related AE requiring intubation, including Grade 4 encephalopathy requiring intubation for airway protection * Any sequenced therapy-related Grade 5 event
Time frame: First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.
Population: DLT evaluable set included all participants treated in the Phase 1 dosing cohort who received the target dose of lenzilumab and axicabtagene ciloleucel and were followed for at least 28 days after the anti-CD19 CAR T cell infusion or who received a dose of lenzilumab lower than target dose for that cohort and experienced a DLT during the 28-day after the anti-CD19 CAR T cell infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene | 0 percentage of participants |
| Phase 1/Cohort 2 | Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene | 0 percentage of participants |
Primary
Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration
Time frame: Up to 28 days
Population: Due to early termination of study, Phase 2 of the study was not conducted.
Secondary
Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood
Peak is defined as the maximum number of CAR T cells in blood measured after the axicabtagene ciloleucel infusion.
Time frame: Baseline up to Month 3
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood | 74.28 cells/μL | Standard Deviation 97.6 |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood | 20.35 cells/μL | Standard Deviation 15.12 |
Secondary
Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators
CR rate: percentage of participants with CR (CMR;CRR). CMR: positron emission tomography(PET)5-point scale(5PS) scores of 1(no uptake above background), 2(uptake ≤ mediastinum), 3(uptake \> mediastinum but ≤ liver) with/without a residual mass); no new sites; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter (LDi) of a lesion; no extra lymphatic sites; absent non-measured lesion;organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.
Time frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators | 67 percentage of participants |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators | 67 percentage of participants |
Secondary
Phase 1 and Phase 2: Duration of Response (DOR) in Participants Who Experience an Objective Response Per IWG Lugano Classification as Determined by Study Investigators
DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause. Objective response is defined in outcome measure (OM) 7.
Time frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
Population: For Phase 1, participants in the Safety Analysis Set with available data were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Duration of Response (DOR) in Participants Who Experience an Objective Response Per IWG Lugano Classification as Determined by Study Investigators | 9.9 Months |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Duration of Response (DOR) in Participants Who Experience an Objective Response Per IWG Lugano Classification as Determined by Study Investigators | 12.1 Months |
Secondary
Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators
ORR: Percentage of participants with CR(CMR;CRR) or PR(partial metabolic response(PMR);partial radiologic response (PRR)).CMR:PET 5PS scores of 1,2,3 with/without a residual mass;no new sites;no evidence of FDG-avid disease in bone marrow.CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in LDi of a lesion;no extra lymphatic sites;absent non-measured lesion;organ enlargement regress to normal;no new sites;bone marrow normal by morphology.PMR:5PS scores of 4(uptake moderately higher than liver),or 5(uptake markedly higher than liver and/or new lesions),with reduced uptake compared to baseline and residual masses of any size;no new sites;residual update \> update in normal bone marrow but reduced compared with baseline.PRR:≥ 50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites;absent/normal, regressed, but no increase of nonmeasured lesions;spleen regressed by \> 50% in length beyond normal;no new sites.
Time frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators | 67 percentage of participants |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators | 100 percentage of participants |
Secondary
Phase 1 and Phase 2: Overall Survival (OS)
OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Time frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
Population: Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Overall Survival (OS) | 10.8 Months |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Overall Survival (OS) | 13.0 Months |
Secondary
Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events
Time frame: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events | 100 percentage of participants |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events | 100 percentage of participants |
Secondary
Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome
Time frame: Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome | 67 percentage of participants |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome | 67 percentage of participants |
Secondary
Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events
Time frame: Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events | 100 percentage of participants |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events | 67 percentage of participants |
Secondary
Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events
Time frame: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events | 67 percentage of participants |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events | 100 percentage of participants |
Secondary
Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1
Peak is defined as the maximum post-baseline level of the analyte from baseline to Week 4.
Time frame: Baseline up to Week 4
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | CXCL10 | 2000.00 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | Granzyme B | 14.50 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IFN-gamma | 1238.30 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-1 RA | 4984.00 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-2 | 11.80 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-6 | 22.50 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-8 | 56.70 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | TNF alpha | 5.50 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | GM-CSF | 1.90 pg/mL |
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | MCP-1 | 1178.10 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | TNF alpha | 3.00 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | CXCL10 | 809.40 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-6 | 13.10 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | Granzyme B | 11.80 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | MCP-1 | 866.80 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IFN-gamma | 45.70 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-8 | 31.50 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-1 RA | 919.00 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | GM-CSF | 1.90 pg/mL |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1 | IL-2 | 18.20 pg/mL |
Secondary
Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators
PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause.
Time frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
Population: For Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1/Cohort 1 | Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators | 10.8 Months |
| Phase 1/Cohort 2 | Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators | 13.0 Months |