Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

• ClinicalTrials.gov Identifier: NCT05066165
• Recruitment Status: Terminated
• First Posted: October 4, 2021
• Results First Posted: December 28, 2023
• Last Update Posted: December 28, 2023
• Sponsor: Intellia Therapeutics
• Information provided by (Responsible Party): Intellia Therapeutics

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia
• Interventions: Genetic: Arm 1: NTLA-5001; Genetic: Arm 2: NTLA-5001
• Enrollment: 6

Participant Flow

Recruitment Details	A total of 6 participants were enrolled at 3 sites in one country. A total of 2 participants received the product at Dose Level 1 in the Dose Escalation phase. The first participant was enrolled on 17 December 2021 and the last participant was enrolled on 21 July 2022. Dose escalation phase did not proceed beyond Dose Level 1. Dose Expansion phase was not initiated.
Pre-assignment Details	Six participants were enrolled in the study (signed informed consent and underwent leukapheresis), but only two participants were dosed (administered Dose Level 1).

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Period Title: C1:DoseLevel1 Assignment
Started	1	5
Completed	1	1
Not Completed	0	4
Reason Not Completed
Pivoting to an allogeneic version of this program	0	4
Period Title: C1:DoseLevel1 Dosed Participants (W1-16)
Started	1	1
Completed	0	0
Not Completed	1	1
Reason Not Completed
Death	1	1
Period Title: Cohort2:Dose Level 2
Started	0	0
Completed	0	0
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow	Total
Arm/Group Description		Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy.	Total of all reporting groups
Overall Number of Baseline Participants		1	5	6
Baseline Analysis Population Description		Five participants were enrolled in Arm 2, but only one was dosed.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	1 participants	5 participants	6 participants
		68; (68 to 68)	57; (41 to 74)	59; (41 to 74)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	5 participants	6 participants
	Female	0 0.0%	2 40.0%	2 33.3%
	Male	1 100.0%	3 60.0%	4 66.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	5 participants	6 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	1 100.0%	5 100.0%	6 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	5 participants	6 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	1 100.0%	5 100.0%	6 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	1 participants	5 participants	6 participants
		1 100.0%	5 100.0%	6 100.0%
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	1 participants	5 participants	6 participants
		37.7 (0)	24.3 (6.63)	26.5 (8.07)
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	1 participants	5 participants	6 participants
		190.0 (0)	170.2 (9.18)	173.5 (11.52)
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	1 participants	5 participants	6 participants
		136.0 (0)	71.3 (24.79)	82.1 (34.50)

Outcome Measures

1. Primary Outcome

Title	Participants That Experienced Dose-limiting Toxicities (DLTs)
Description	DLTs were defined as events with onset within 28 days of infusion. AEs were collected from time of informed consent through the Week 112 visit. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. Severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 toxicity grading criteria. The measure reported below for the primary outcome consists of DLT data only. Adverse events are reported in the Adverse Event section of this presentation.
Time Frame	Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for this presentation.

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description:	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Overall Number of Participants Analyzed	1	1
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

2. Secondary Outcome

Title	Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood
Description	Frequency of edited TCR transgene copy number in the peripheral blood of the participants was determined by droplet digital polymerase chain reaction (ddPCR).
Time Frame	From NTLA-5001 infusion up to 4 weeks post-infusion

Outcome Measure Data

Analysis Population Description

The Cell Kinetics Analysis Set (defined as all participants who received NTLA-5001 and have at least one evaluable cell kinetics sample) was used for this presentation.

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description:	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Overall Number of Participants Analyzed	1	1
Mean (Standard Deviation); Unit of Measure: copy/ng gDNA
	NA [1] (NA)	NA [1] (NA)

[1]

Transgene in all collected patients' samples were below limit of quantification or negative

3. Secondary Outcome

Title	Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood
Description	Persistence of edited TCR transgene copy in the peripheral blood of the participants determined by ddPCR.
Time Frame	From NTLA-5001 infusion up to 4 weeks post-infusion

Outcome Measure Data

Analysis Population Description

The Cell Kinetics Analysis Set (defined as all participants who received NTLA-5001 and have at least one evaluable cell kinetics sample) was used for this presentation.

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description:	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Overall Number of Participants Analyzed	1	1
Measure Type: Number; Unit of Measure: Days
	NA [1]	NA [1]

[1]

Transgene levels and Persistence were not quantifiable, as no participant had measurable values for edited TCR transgene copies

4. Secondary Outcome

Title	Tumor Response in Participants With AML
Description	Rate of objective response, where response is complete response without measurable residual disease (CRMRD-) (Arm 1). Rate of objective response, where response is CRMRD-, complete response, complete remission with incomplete hematologic recovery, morphologic leukemia-free state, and partial remission (Arm 2).
Time Frame	From NTLA-5001 infusion up to 4 weeks post-infusion

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for presentations of disease response data.

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description:	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Overall Number of Participants Analyzed	1	1
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

5. Secondary Outcome

Title	Response Duration in Participants With AML
Description	Bone marrow results were planned to be used to determine the duration of response / remission (DOR) for subjects with objective response, from first response until MRD was measured above the lower level of detection for the central laboratory assay, or death from any cause, whichever occurred first (Arm 1). Bone marrow results were planned to be used to determine DOR for subjects with composite CR, from first response to progression or death due to any cause, whichever occurred first (Arm 2).
Time Frame	From NTLA-5001 infusion up to 4 weeks post-infusion

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for presentations of disease response data.

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description:	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Overall Number of Participants Analyzed	1	1
Median (Standard Deviation); Unit of Measure: Weeks
	NA [1] (NA)	NA [1] (NA)

[1]

Both participants experienced disease progression at the first assessment

6. Secondary Outcome

Title	Disease Progression in Participants With AML
Description	Bone marrow results were used to determine the time to clinical progression. Progressive disease was defined as an increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells
Time Frame	From NTLA-5001 infusion up to 4 weeks post-infusion

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (defined as all participants who received NTLA-5001) was used for presentations of disease response data.

Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description:	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
Overall Number of Participants Analyzed	1	1
Median (Standard Deviation); Unit of Measure: Weeks
	NA [1] (NA)	NA [1] (NA)

[1]

Both participants experienced disease progression at the first assessment

Adverse Events

Time Frame	From the date of NTLA-5001 infusion up to 16 weeks post-infusion.
Adverse Event Reporting Description	Safety population = all participants who received NTLA-5001.
Arm/Group Title	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
Arm/Group Description	Arm 1: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.	Arm 2: NTLA-5001: Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy. The participant was administered Dose Level 1.
All-Cause Mortality
	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/1 (100.00%)	1/1 (100.00%)
Serious Adverse Events
	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/1 (0.00%)	1/1 (100.00%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	0/1 (0.00%)	1/1 (100.00%)
Nervous system disorders
Headache † 1	0/1 (0.00%)	1/1 (100.00%)
1 Term from vocabulary, MedDRA version 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow	Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/1 (100.00%)	1/1 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/1 (0.00%)	1/1 (100.00%)
Cardiac disorders
Sinus tachycardia † 1	0/1 (0.00%)	1/1 (100.00%)
Gastrointestinal disorders
Constipation † 1	0/1 (0.00%)	1/1 (100.00%)
General disorders
Fatigue † 1	1/1 (100.00%)	0/1 (0.00%)
Chills † 1	1/1 (100.00%)	0/1 (0.00%)
Infections and infestations
Herpes simplex reactivation † 1	0/1 (0.00%)	1/1 (100.00%)
Injury, poisoning and procedural complications
Contusion † 1	1/1 (100.00%)	0/1 (0.00%)
Procedural pain † 1	1/1 (100.00%)	0/1 (0.00%)
Investigations
International normalised ratio increased † 1	0/1 (0.00%)	1/1 (100.00%)
Lymphocyte count decreased † 1	1/1 (100.00%)	0/1 (0.00%)
Platelet count decreased † 1	1/1 (100.00%)	1/1 (100.00%)
White blood cell count decreased † 1	0/1 (0.00%)	1/1 (100.00%)
Metabolism and nutrition disorders
Hypoalbuminaemia † 1	1/1 (100.00%)	1/1 (100.00%)
Hypophosphataemia † 1	0/1 (0.00%)	1/1 (100.00%)
Hyponatraemia † 1	0/1 (0.00%)	1/1 (100.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/1 (100.00%)	0/1 (0.00%)
Psychiatric disorders
Hallucination † 1	1/1 (100.00%)	0/1 (0.00%)
Affect lability † 1	1/1 (100.00%)	0/1 (0.00%)
Abnormal dreams † 1	1/1 (100.00%)	0/1 (0.00%)
Renal and urinary disorders
Haematuria † 1	1/1 (100.00%)	0/1 (0.00%)
Proteinuria † 1	0/1 (0.00%)	1/1 (100.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/1 (100.00%)	0/1 (0.00%)
Skin and subcutaneous tissue disorders
Skin ulcer † 1	1/1 (100.00%)	0/1 (0.00%)
Skin mass † 1	1/1 (100.00%)	0/1 (0.00%)
Vascular disorders
Hypertension † 1	1/1 (100.00%)	0/1 (0.00%)
1 Term from vocabulary, MedDRA version 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

The study was terminated by the Sponsor due to a strategic business decision.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Trial Manager
• Organization: Intellia Therapeutics
• Phone: 833-888-0387
• EMail: clinicalscience@intelliatx.com

• Responsible Party: Intellia Therapeutics
• ClinicalTrials.gov Identifier: NCT05066165
• Other Study ID Numbers: ITL-5001-CL-001
• First Submitted: September 23, 2021
• First Posted: October 4, 2021
• Results First Submitted: August 31, 2023
• Results First Posted: December 28, 2023
• Last Update Posted: December 28, 2023