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

Tracking Information

• First Submitted Date: September 23, 2021
• First Posted Date: October 4, 2021
• Results First Submitted Date: August 31, 2023
• Results First Posted Date: December 28, 2023
• Last Update Posted Date: December 28, 2023
• Actual Study Start Date: December 17, 2021
• Actual Primary Completion Date: July 21, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2023)

Participants That Experienced Dose-limiting Toxicities (DLTs) [ Time Frame: Primary DLT assessment from NTLA-5001 infusion up to 28 days post-infusion ]

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.

• Original Primary Outcome Measures (submitted: September 23, 2021): Safety and tolerability as determined by adverse events (AEs) and dose-limiting toxicities (DLTs) (dose escalation only) [ Time Frame: From NTLA-5001 infusion up to week 112 post-infusion, primary DLT assessment up to 28 days post-infusion ]

Current Secondary Outcome Measures (submitted: October 27, 2023)

• Frequency of NTLA-5001 T-cell Receptor (TCR) Transgene Copy Number in the Peripheral Blood [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
  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 NTLA-5001 T Cell Receptor (TCR) Transgene Copy in Peripheral Blood [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
  Persistence of edited TCR transgene copy in the peripheral blood of the participants determined by ddPCR.
• Tumor Response in Participants With AML [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
  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).
• Response Duration in Participants With AML [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
  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).
• Disease Progression in Participants With AML [ Time Frame: From NTLA-5001 infusion up to 4 weeks post-infusion ]
  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

Original Secondary Outcome Measures (submitted: September 23, 2021)

• To characterize cell kinetics of NTLA-5001 via frequency and persistence of NTLA 5001 T cell receptor (TCR) transgene copy [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]
• To estimate the antitumor activity of NTLA-5001 in participants with AML via tumor response, response duration, and disease progression [ Time Frame: From NTLA-5001 infusion up to 112 weeks post-infusion ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
• Official Title: Phase 1/2a, Single Dose Study Investigating NTLA-5001 in Subjects With Acute Myeloid Leukemia
• Brief Summary: 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).
• Detailed Description: 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia

Intervention

• Genetic: Arm 1: NTLA-5001

  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.

• Genetic: Arm 2: NTLA-5001

  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.

Study Arms

• Experimental: Arm 1: NTLA-5001
  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.
  Intervention: Genetic: Arm 1: NTLA-5001
• Experimental: Arm 2: NTLA-5001
  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.
  Intervention: Genetic: Arm 2: NTLA-5001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 13, 2022): 6
• Original Estimated Enrollment (submitted: September 23, 2021): 54
• Actual Study Completion Date: August 31, 2022
• Actual Primary Completion Date: July 21, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria (abbreviated):

• Has AML as defined by World Health Organization
• Has detectable disease following first-line therapy
• Is ≥ 18 years of age.
• Carries the human leukocyte antigen-A0201 (HLA-A*02:01) allele.
• Has ECOG performance status of 0 to 1.
• Has adequate absolute total lymphocyte count
• Has adequate cardiac, renal, and liver organ function

Exclusion Criteria (abbreviated):

• Has received AML-directed therapy or immunomodulatory therapy within a specified window prior to study entry.
• Has received allogeneic hematopoietic cell transplant within 84 days, with ongoing GVHD, with recent DLI, or on active immunosuppression.
• Has CNS involvement by tumor.
• Has severe autoimmunity requiring immunomodulatory therapy.
• Has active disseminated intravascular coagulation (DIC), bleeding or coagulopathy.
• Has leukocytosis ≥ 20,000 blasts/μL despite hydroxyurea or has rapidly progressive disease
• Has human immunodeficiency virus (HIV) infection, or any uncontrolled infection.
• Female subjects are pregnant or breastfeeding; or are of childbearing potential and are unwilling to use protocol specified method of contraception.
• Male subjects who have female partners of childbearing potential and are unwilling to use protocol specified method of contraception.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT05066165
• Other Study ID Numbers: ITL-5001-CL-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Intellia Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Intellia Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Intellia Therapeutics
• Verification Date: December 2023