Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Immunoproliferative Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count \<5%, administered by IV infusion following lymphodepleting chemotherapy.

Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count ≥5%, administered by IV infusion following lymphodepleting chemotherapy.

Autologous WT1-directed TCR T cells engineered ex vivo using CRISPR/Cas9 as intravenous infusion after pre-conditioning chemotherapy.

Cyclophosphamide and Fludarabine will be administered on Day -5, -4, and -3 as intravenous infusion.

Arm 1: NTLA-5001

Arm 2: NTLA-5001

This study will be conducted to evaluate the safety, tolerability, cellular kinetics (CK), activity, and pharmacodynamics (PD) of NTLA-5001 in participants with Acute Myeloid Leukemia (AML).

This 2-part first in human (FIH) study is comprised of two open-label arms. It is a multi-center, Phase 1/2a study evaluating the safety and activity of NTLA-5001 in subjects with persistent or recurrent Acute Myeloid Leukemia after first-line or later therapy.

Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia

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.

Frequency of edited TCR transgene copy number in the peripheral blood of the participants was determined by droplet digital polymerase chain reaction (ddPCR).

Persistence of edited TCR transgene copy in the peripheral blood of the participants determined by ddPCR.

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).

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).

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

Intellia Therapeutics

Safety population = all participants who received NTLA-5001.

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 1: NTLA-5001 Participants With AML Blasts < 5% of Bone Marrow

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.

Arm 2: NTLA-5001 Participants With AML Blasts ≥ 5% of Bone Marrow

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

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body Mass Index

Height

Weight

Five participants were enrolled in Arm 2, but only one was dosed.

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

Trial Manager

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

Participants That Experienced Dose-limiting Toxicities (DLTs)

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.

Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood

Persistence of NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood

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

Spots Global Cancer Trial Database for clustered regularly interspaced short palindromic repeats