Trial Outcomes & Findings for Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma (NCT NCT04314843)

Last Updated: 2024-03-04

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

6 participants

Primary outcome timeframe

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

Results posted on

2024-03-04

Participant Flow

Participants were enrolled at study sites in the United States.

9 participants were screened. The study was terminated earlier than planned, and thus the study did not proceed to Phase 2.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	3	3
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Death	2	2
Overall Study Rolled over to long-term follow-up study after study terminated	1	1

Baseline Characteristics

Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	62 years STANDARD_DEVIATION 15.7 • n=5 Participants	65 years STANDARD_DEVIATION 10.2 • n=7 Participants	64 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
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	0 percentage of participants

PRIMARY outcome

Timeframe: Up to 28 days

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events	67 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome	67 percentage of participants	67 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events	100 percentage of participants	67 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
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 Interval 9.0 to 99.0	67 percentage of participants Interval 9.0 to 99.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators	67 percentage of participants Interval 9.0 to 99.0	100 percentage of participants Interval 29.0 to 100.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=2 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
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 The lower and upper limit of Confidence Interval (CI) was not estimable due to insufficient number of participants with an event.	12.1 Months Interval 2.7 to The upper limit of CI was not estimable due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators	10.8 Months Interval 0.9 to The upper limit of Confidence Interval (CI) was not estimable due to insufficient number of participants with an event.	13.0 Months Interval 3.6 to The upper limit of CI was not estimable due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Overall Survival (OS)	10.8 Months Interval 4.6 to The upper limit of Confidence Interval (CI) was not estimable due to insufficient number of participants with an event.	13.0 Months Interval 3.6 to The upper limit of CI was not estimable due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: 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.

Peak is defined as the maximum post-baseline level of the analyte from baseline to Week 4.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
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 Interval 3.4 to 16.5	3.00 pg/mL Interval 1.7 to 3.3
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 Interval 1.9 to 1.9	1.90 pg/mL Interval 1.9 to 1.9
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 Interval 1474.5 to 2000.0	809.40 pg/mL Interval 448.6 to 1298.1
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 Interval 9.2 to 44.2	11.80 pg/mL Interval 2.6 to 17.8
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 Interval 90.6 to 1426.0	45.70 pg/mL Interval 7.5 to 151.5
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 Interval 4038.0 to 6187.0	919.00 pg/mL Interval 701.0 to 1099.0
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 Interval 6.3 to 22.7	18.20 pg/mL Interval 2.5 to 21.1
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 Interval 8.0 to 976.0	13.10 pg/mL Interval 3.0 to 15.4
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 Interval 12.9 to 75.7	31.50 pg/mL Interval 15.4 to 39.9
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 Interval 1007.0 to 1300.0	866.80 pg/mL Interval 589.9 to 968.9

SECONDARY outcome

Timeframe: 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.

Peak is defined as the maximum number of CAR T cells in blood measured after the axicabtagene ciloleucel infusion.

Outcome measures

Outcome measures
Measure	Phase 1/Cohort 1 n=3 Participants 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.	Phase 1/Cohort 2 n=3 Participants 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.
Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood	74.28 cells/μL Standard Deviation 97.60	20.35 cells/μL Standard Deviation 15.12

Adverse Events

Phase 1/Cohort 1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase 1/Cohort 2

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1/Cohort 1 n=3 participants at risk 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.	Phase 1/Cohort 2 n=3 participants at risk 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.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
General disorders Pyrexia	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Infections and infestations Covid-19	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Infections and infestations Covid-19 pneumonia	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Infections and infestations Pneumonia	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Investigations Platelet count decreased	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Metabolism and nutrition disorders Hyponatraemia	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Nervous system disorders Aphasia	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Nervous system disorders Disturbance in attention	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Nervous system disorders Encephalopathy	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	66.7% 2/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Psychiatric disorders Agitation	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Vascular disorders Hypertension	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.
Vascular disorders Hypotension	33.3% 1/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.	0.00% 0/3 • Adverse Events: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion. All-Cause Mortality: Enrollment up to 22.5 months Adverse Events and All-Cause Mortality: The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel and/or any dose of lenzilumab.

Other adverse events

Additional Information

Medical Information

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