A Study of NT-112 in HLA-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/ or Metastatic Solid Tumors Positive for the KRAS G12D Mutation

• ClinicalTrials.gov Identifier: NCT06218914
• Recruitment Status: Recruiting
• First Posted: January 23, 2024
• Last Update Posted: April 2, 2024
• Sponsor: Neogene Therapeutics, Inc.
• Information provided by (Responsible Party): Neogene Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 9, 2024
• First Posted Date: January 23, 2024
• Last Update Posted Date: April 2, 2024
• Actual Study Start Date: February 5, 2024
• Estimated Primary Completion Date: August 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2024)

• Evaluate the safety of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors; evaluation of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D(s)) [ Time Frame: 28 days after infusion ]
  Incidence of dose-limiting toxicities
• Adverse events and Serious adverse events [ Time Frame: Up to 24 months post-infusion ]
  Incidence of adverse events and serious adverse events by dose level

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 18, 2024)

• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.
• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.
• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.
• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.
• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
• Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors [ Time Frame: Up to 24 months post-infusion ]
  Overall survival (OS)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of NT-112 in HLA-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/ or Metastatic Solid Tumors Positive for the KRAS G12D Mutation
• Official Title: An Open-label, Phase 1, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor Activity of NT-112 in Human Leukocyte Antigen-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for the KRAS G12D Mutation
• Brief Summary: Phase I Study of NT-112, an autologous T-cell therapy product genetically engineered to express an HLA-C*08:02-restricted T cell receptor (TCR), targeting KRAS G12D mutant solid tumors.
• Detailed Description: This is a Phase 1, open-label, multicenter study to evaluate the safety and preliminary antitumor activity of NT-112 in HLA-C*08:02 subjects with unresectable, advanced, and/or metastatic NSCLC, colorectal adenocarcinoma, pancreatic adenocarcinoma, endometrial cancer, or any other solid tumor histology that is positive for the KRAS G21D mutation.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-small Cell Lung Cancer
• Colorectal Carcinoma
• Pancreatic Ductal Adenocarcinoma
• Endometrial Cancer
• Solid Tumor, Adult
• KRAS G12D

Intervention

Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12D

• Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
• Single infusion of T cell receptor (TCR) T cells
• Post-infusion recombinant interleukin-2 (rIL-2)

Study Arms

Experimental: NT-112

Dose Escalation of NT-112.

Intervention: Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12D

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2024): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2, 2040
• Estimated Primary Completion Date: August 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Age ≥18 years
• Diagnosed with NSCLC, Colorectal adenocarcinoma, Pancreatic adenocarcinoma, Endometrial Cancer or any other solid tumor
• Tumors must harbor a KRAS G12D variant mutation and subject must be HLA-C*08:02 positive
• Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
• Presence of at least 1 measurable lesion per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment

Key Exclusion Criteria:

• Any other primary malignancy within the 3 years prior to enrollment (except for non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or low-grade prostate cancer
• Known, active primary central nervous system (CNS) malignancy
• History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
• History of stroke or transient ischemic attack within the 12 months prior to enrollment.
• History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
• Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
• Any form of primary immunodeficiency.
• Active immune-mediated disease requiring systemic steroids or other immunosuppressive treatment (except if related to prior checkpoint inhibitor therapy)
• Female of childbearing potential who is lactating or breast feeding at the time of enrollment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Neogene Medical Affairs; (310) 742-9929; MedicalAffairs@neogene.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06218914
• Other Study ID Numbers: NT-112-301
• Has Data Monitoring Committee: Yes

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

• Plan to Share IPD: No

• Current Responsible Party: Neogene Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Neogene Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Neogene Therapeutics, Inc.
• Verification Date: April 2024