CT275 / 15 - Phase 1 clinical update of allogeneic invariant natural killer T cells (iNKTs), agenT-797, alone or in combination with pembrolizumab or nivolumab in patients with advanced solid tumors

B Carneiro

Document Type

Abstract

Publication Date

4-18-2023

Publication Title

AACR Annual Meeting April 14-19; Orlando, FL. 2023: CT275.

Keywords

oregon; chiles

Abstract

Introduction: AgenT-797 is an allogeneic iNKT cell therapy and represents a novel, scalable, off-the-shelf approach against solid tumors. iNKTs are a unique subset of T cells, that mediate antitumor responses by direct killing, targeting CD1d and other ligands in the tumor microenvironment, and by activating host immune cells. We conducted a clinical trial to investigate agenT-797 activity as single agent and in combination (combo) with PD-1 blockade after prior progression on PD-1 therapy.
Methods: Patients (pts) with relapsed or refractory solid tumors were treated with single IV infusion of agenT-797 (no lymphodepletion) at 4.3 x 10^6 or 1.4 x 10^7 cells/kg, as monotherapy or in combo with pembrolizumab (pembro) or nivolumab (nivo). Dose escalation followed 3+3 scheme. Endpoints included safety, persistence of agenT-797, objective responses, duration of response, progression-free survival, and time to response. Adverse events (AEs) were reported per CTCAE v5.0. Dose limiting toxicities (DLTs) were evaluated. AgenT-797 persistence was assessed by assays utilizing SNPs and cfDNA analysis. Serum biomarkers were measured with MSD V-PLEX cytokine assays. On-treatment tumor biopsy was obtained for multiplex immunofluorescence staining and next generation sequencing.
Results: As of February 5th, 32 pts (median age 62y, range 30-83) were treated with agenT-797 monotherapy (n=26) or combo (n=6) with pembro or nivo. Pts had median 4 lines of prior therapy (range 1-13). Tumor types included pancreatic (6), NSCLC (4), rectal (4), cholangiocarcinoma/biliary duct (4), and other (14)*. Tolerability was favorable, with no cytokine release syndrome, neurotoxicity, and no DLTs. Treatment-related AEs included 16.7% (5) grade 1, 3.3% (1) grade 2, and 3.3% (1) grade 3 (anemia). At data cutoff, agenT-797 monotherapy and combo revealed early clinical activity. Among 29 evaluable pts, a confirmed partial response in MSI-H gastric cancer refractory to PD-1 treated with agenT-797 + nivo (remains ongoing >6 months) and 8 pts had stable disease (SD). Prolonged SD (>3 months) for 3 monotherapy pts. Overall response rate 20% (1/5) for pts treated with agenT-797 + pembro or nivo. AgenT-797 was detected in peripheral blood up to day 8 post infusion. Preliminary data identified transient increase in serum IFNgamma levels day 2 post infusion.
Conclusion: AgenT-797 was well tolerated as monotherapy and in combo with PD-1 (pembro or nivo). Anti-tumor activity in combo with nivo was observed in gastric cancer. Results support the potential of a novel therapeutic strategy employed by agenT-797 to enhance antitumor immunity in PD-1 refractory tumors. Enrollment ongoing and correlative studies will be presented. *PD-1 refractory NSCLC, pancreatic, rectal, cholangiocarcinoma, cervical, gastric, ocular melanoma, renal, and upper tract urothelial

Clinical Institute

Cancer

Department

Oncology

Department

Earle A. Chiles Research Institute

Comments

Carneiro B, Garmezy B, Hamm JT, Sanborn RE, Wise-Draper T, Khoueiry AE-, Wilky B, Hoon DSB, Buffa A, Michelet X, Purbhoo M, Exley MA, Einstein D

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