Study of Lenzilumab and Axicabtagene Ciloleucel in Partic... | NCT04314843

ID	Type	Description	Link
2019-004568-23	EudraCT Number

Name	Class
Humanigen, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Lenzilumab and Axicabtagene Ciloleucel	Experimental	Phase 1: Participants will receive cyclophosphamide and fludarabine lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab and axicabtagene ciloleucel on Day 0 to determine a recommended Phase 2 dose (RP2D) of lenzilumab. Phase 2: Participants will receive cyclophosphamide and fludarabine lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab, at the RP2D, and axicabtagene ciloleucel on Day 0.	Drug: Cyclophosphamide Drug: Fludarabine Biological: Lenzilumab Biological: Axicabtagene Ciloleucel

Name	Type	Description	Arm Group Labels	Other Names
Cyclophosphamide	Drug	Administered according to package insert	Lenzilumab and Axicabtagene Ciloleucel

Measure	Description	Time Frame
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	First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.
Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration		Up to 28 days

Measure	Description	Time Frame
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: Percentage of Participants Experiencing Serious Adverse Events		Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

Eligibility Module

Eligibility 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/Exclusion criteria may apply.

Name	Affiliation	Role
Kite Study Director	Kite, A Gilead Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Stanford University		Palo Alto	California	94305	United States
Moffitt Cancer Center

PubMed Identifier	Type	Citation	Retractions
	Background	Kenderian, S. S., Oluwole, O. O., Mccarthy, P. L., Reshef, R., Shiraz, P., Ahmed, O., Le Gall, J., Nahas, M., Tang, L. And Neelapu, S. S. Zuma-19: A Phase 1/2 Multicenter Study of Lenzilumab Use With Axicabtagene Ciloleucel (Axi-Cel) In Patients (Pts) With Relapsed Or Refractory Large B Cell Lymphoma (R/R Lbcl). Blood 136(Supplement 1): 6-7, (2020). Conference Proceedings.
	Background	Olalekan O. Oluwole, MBBS, Saad S. Kenderian, MD, Parveen Shiraz, MD, Reem Karmali, MD, MSc, Ran Reshef, MD, MSc, Philip L. McCarthy, MD, Nilanjan Ghosh, MD, PhD, Aleksandr Lazaryan, MD, PhD, MPH, Simone Filosto, PhD, Soumya Poddar, PhD, Daqin Mao, PhD, Andrew Peng, MS, Adrian Kilcoyne, MD, MPH, Myrna Nahas, MD, Sattva S. Neelapu, MD. A Phase 1/2 Study of Axicabtagene Ciloleucel Plus Lenzilumab in Patients With Relapsed or Refractory Large B-Cell Lymphoma. American Society of Hemotology; Dec 10-13, 2022; New Orleans, LA. Abstract 4635

Label	URL
Gilead Clinical Trials Website	View source

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 3, 2021	May 19, 2023

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

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.

Posted

Number

percentage of participants

First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG0003 OG0013

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Primary

Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration

Due to early termination of study, Phase 2 of the study was not conducted.

Posted

Up to 28 days

ID	Title	Description
OG000	Phase 2	Participants were to received 500 mg/m^2 cyclophosphamide IV and 30 mg/m^2/day fludarabine IV lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab IV (at RP2D, dose selected based on Phase 1) and axicabtagene ciloleucel IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg but the study was terminated before proceeding to Phase 2.

Units	Counts
Participants	OG000

Secondary

Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events

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.

Posted

Number

percentage of participants

Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events

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.

Posted

Number

percentage of participants

Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome

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.

Posted

Number

percentage of participants

Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events

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.

Posted

Number

percentage of participants

Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

ID	Title	Description
OG000	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.
OG001

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

ID	Title	Description
OG000	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.

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.

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.

Posted

Median

95% Confidence Interval

Months

First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Median

95% Confidence Interval

Months

First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Phase 1 and Phase 2: Overall Survival (OS)

OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

Phase 1, participants in the Safety Analysis Set were analyzed. Due to early termination of study, Phase 2 of the study was not conducted.

Posted

Median

95% Confidence Interval

Months

First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Median

Inter-Quartile Range

pg/mL

Baseline up to Week 4

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Mean

Standard Deviation

cells/μL

Baseline up to Month 3

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Covid-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Covid-19 pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected3 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Platelet count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Aphasia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Disturbance in attention	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected3 at risk
Agitation	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Hypotension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected3 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0003 affected3 at risk EG0011 affected3 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Bradycardia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Sinus arrhythmia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected3 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Dry eye	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Photophobia	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Vision blurred	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected3 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected3 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 affected3 at risk EG0011 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0002 affected3 at risk EG0011 affected3 at risk
Malaise	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected3 at risk
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Pain	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0002 affected3 at risk EG0012 affected3 at risk
Tenderness	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Candida infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Cytomegalovirus infection reactivation	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Pharyngitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Skin infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Neutrophil count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0003 affected3 at risk EG0012 affected3 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0013 affected3 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Diffuse large B-cell lymphoma refractory	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Cognitive disorder	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Dysgraphia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0002 affected3 at risk EG0010 affected3 at risk
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected3 at risk
Seizure	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Tremor	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected3 at risk
Confusional state	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Delirium	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Depression	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Insomnia	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Nocturia	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk
Hypotension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected3 at risk
Thrombosis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk

ID	Term
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	2	3	2	3	3	3
EG001	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.	2	3	3	3	3	3

ID	Term
D003520	Cyclophosphamide
C024352	fludarabine
C000710968	lenzilumab
C000629083	axicabtagene ciloleucel