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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Tumor, Solid

Intervention / Treatment
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* Drug: agenT-797
* Drug: Approved ICIs


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Monotherapy with agenT-797<br>3+3 Dose escalation of agenT-797 will be administered as a single intravenous (IV) infusion. | Drug: agenT-797<br>* 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.<br>|
| Experimental: Part 2: agenT-797 in Combination with approved ICIs<br>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<br>* 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.<br>Drug: Approved ICIs<br>* Nivolumab and pembrolizumab<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor, Immunotherapy, iNKT cells, Tumor