A Study Investigating agenT-797 in Participants With Relapsed/Refractory Solid Tumors

A Phase 1, Open-Label Study of the Safety, Tolerability and Preliminary Clinical Activity of Allogeneic Invariant Natural Killer T (iNKT) Cells (agenT-797) as a Single Agent and in Combination With Approved Immune Checkpoint Inhibitors in Patients With Relapsed/ Refractory Solid Tumors

This is a Phase 1, open-label study to explore the safety, tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT cell therapy, in participants with relapsed/refractory (r/r) solid tumors, as well as define the recommended phase II dose in solid tumors. This Phase 1 study will also explore the safety, tolerability, and preliminary clinical activity of agenT-797 in combination with approved immune checkpoint inhibitors (ICIs), including pembrolizumab and nivolumab, in participants with r/r solid tumors.

Study Overview

• Status: Completed
• Conditions: Tumor, Solid
• Intervention / Treatment: Drug: agenT-797; Drug: Approved ICIs

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Cancer Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan - Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological or cytological evidence of relapsed or refractory solid tumor malignancy for which no standard therapy is available or standard therapy has failed
• Measurable disease per RECIST 1.1 as assessed by local site Investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Part 2 only, participants must have progressed per Investigator assessment on pembrolizumab or nivolumab, and agree and are able to continue on the inhibitor(s) while on study
• No other medical, surgical, or psychiatric condition (including active substance abuse) that would interfere with compliance to the protocol, as determined by the Principal Investigator

Exclusion Criteria:

• Concurrent invasive malignancy
• Brain and/or leptomeningeal metastases that are untreated or require current therapy
• Prior radiotherapy within 2 weeks of start of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Monotherapy with agenT-797; 3+3 Dose escalation of agenT-797 will be administered as a single intravenous (IV) infusion.	Drug: agenT-797; agenT-797 is an off-the-shelf cell therapy consisting of ≥ 95% allogeneic human unmodified iNKT cells isolated from 1 healthy donor mononuclear cell apheresis unit and expanded ex vivo.
Experimental: Part 2: agenT-797 in Combination with approved ICIs; Single prespecified dose of agenT-797 administered by IV infusion in combination with approved ICIs administered in accordance with manufacturer instructions and institutional guidelines as per standard of care	Drug: agenT-797; agenT-797 is an off-the-shelf cell therapy consisting of ≥ 95% allogeneic human unmodified iNKT cells isolated from 1 healthy donor mononuclear cell apheresis unit and expanded ex vivo.; Drug: Approved ICIs; Nivolumab and pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Of Participants With Treatment-emergent Adverse Events (TEAEs)	This will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).	Baseline through 12 months
Number Of Adverse Events (AEs) By The Dose Of iNKT Cell Therapy	This will be determined according to the NCI CTCAE v5.0.	Baseline through 12 months
Number Of TEAEs By The Dose Of iNKT Cell Therapy	This will be determined according to the NCI CTCAE v5.0.	Baseline through 12 months
Severity Grade Of AEs By Dose Of iNKT Cell Therapy	This will be determined according to the NCI CTCAE v5.0.	Baseline through 12 months
Number Of Dose-limiting Toxicities		Baseline through first 14 days after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence Of agenT-797 In Peripheral Blood Samples	This will be measured as a length of time, through collection of peripheral blood mononuclear cells and analysis by flow cytometry.	Baseline/Day 1 (pre-infusion, 5 minutes, 0.25, 0.5, 1, 2, and 4 hours after cell infusion), and on Days 2, 5, 8, 15, 22, and 29; Weeks 6, 8, and 12; and Months 6, 9, and 12
Objective Response Rate (ORR)	For solid tumors, this will be determined per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines and for prostate cancer (not evaluable per RECIST 1.1), Prostate Cancer Working Group 3 (PCWG3) will be used.	Up to 12 months
Duration Of Response (DOR)	For solid tumors, this will be determined per RECIST 1.1 guidelines and for prostate cancer (not evaluable per RECIST 1.1), PCWG3 will be used.	Up to 12 months
Progression-free Survival (PFS)	For solid tumors, this will be determined per RECIST 1.1 guidelines and for prostate cancer (not evaluable per RECIST 1.1), PCWG3 will be used.	Up to 12 months
Incidence Of Panel-reactive Antibody		Baseline/Day 1 (pre-infusion), Day 8, Day 15, Day 29, Week 8, Week 12, Month 6, and end of study visit (up to 12 months)
Incidence Of Donor-specific Antibody		Baseline/Day 1 (pre-infusion), Day 8, Day 15, Day 29, Week 8, Week 12, Month 6, and end of study visit (up to 12 months)

Collaborators and Investigators

• Sponsor: MiNK Therapeutics
• Investigators: Study Director: Medical Director, MiNK Therapeutics

Publications and helpful links

General Publications

• Hadfield MJ, Safran H, Purbhoo MA, Grossman JE, Buell JS, Carneiro BA. Overcoming resistance to programmed cell death protein 1 (PD-1) blockade with allogeneic invariant natural killer T-cells (iNKT). Oncogene. 2024 Mar;43(10):758-762. doi: 10.1038/s41388-024-02948-y. Epub 2024 Jan 29.

Helpful Links

• Nivolumab [Package Insert]. Princeton, NJ: Bristol Myers Squibb Company: 2014.
• Pembrolizumab [Package Insert]. White House Station, NJ: Merck & Co. Inc.; 2014-2021.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Actual): January 2, 2024
• Study Completion (Actual): January 2, 2024

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: November 4, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Solid Tumor; Tumor; iNKT cells
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2021-1306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No