uzatresgene autoleucel (ADP-A2M4CD8)

P2, N=66, Recruiting, Adaptimmune | Trial completion date: Oct 2025 --> Aug 2026 | Trial primary completion date: Oct 2025 --> Aug 2026

P2, N=3, Terminated, Adaptimmune | N=45 --> 3 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Apr 2023; Study was terminated due to difficulty recruiting subjects and lack of efficacy

P1, N=120, Recruiting, Adaptimmune | Trial primary completion date: Sep 2023 --> Dec 2025

Nevertheless, inhibition of immunosuppressive pathways may improve anti-tumor responses; therefore, new SURPASS cohorts include ADP-A2M4CD8 combined with nivolumab or pembrolizumab. Data from additional pts treated by August 2023 will be presented. Conclusions ADP-A2M4CD8 continues to show an acceptable benefit-to-risk profile, including in pts receiving nivolumab combination therapy.

Lymphodepletion chemotherapy (fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days) will be followed by infusion of 1â10x10^9 ADP-A2M4CD8 T-cells. Adverse events will be monitored, with participants followed for 15 years from T-cell infusion. Conclusion SURPASS-3 is initiating in Q2 2023.

P2, N=66, Recruiting, Adaptimmune | Not yet recruiting --> Recruiting | Initiation date: Mar 2023 --> Jun 2023

P2, N=45, Active, not recruiting, Adaptimmune | Trial primary completion date: Apr 2023 --> Dec 2023

Introduction: Affinity-enhanced T-cell receptor (TCR) T-cell therapies targeting the intracellular cancer testis antigen MAGE-A4 have shown encouraging results in adults with advanced solid cancers.1,2 Here we explore how TCR T-cell therapy manufacturing process evolution may modulate the function of ADP-A2M4CD8, the next generation counterpart of afamitresgene autoleucel (afami-cel; formerly ADP-A2M4), using single-cell RNA sequencing (scRNA-seq) and in vitro functional assessment. Whole-transcriptome, single-cell investigation of the cellular subsets produced during manufacturing of afami-cel and ADP-A2M4CD8 indicate that infusion of cells with a less cytotoxic GEP does not prevent broad anti-tumor efficacy and may correspond with beneficial characteristics. 1. Van Tine BA, et al.

P2, N=45, Active, not recruiting, Adaptimmune | Recruiting --> Active, not recruiting | Trial completion date: Oct 2038 --> Dec 2023

Purpose: This abstract presents data on two cell therapies being tested in clinical trials, afamitresgene autoleucel (afami-cel; formerly ADP-A2M4) and its next-generation counterpart ADP-A2M4CD8, to inform nurses on new promising therapies...SURPASS (NCT04044859) is a Phase 1, first-in-human trial evaluating ADP-A2M4CD8 as monotherapy or in combination with nivolumab in multiple tumor types... Nurses play key roles at every stage in the administration of T-cell therapy. Understanding advances in cancer treatment and associated clinical data will better prepare nurses to effectively manage patients that may benefit from these novel therapies.

P1, N=120, Recruiting, Adaptimmune | N=90 --> 120

P2, N=66, Not yet recruiting, Adaptimmune

P1, N=90, Recruiting, Adaptimmune | N=60 --> 90

P1, N=60, Recruiting, Adaptimmune | N=45 --> 60 | Trial primary completion date: Apr 2022 --> Sep 2023

scRNASeq gene expression profiles of first-gen ADP-A2M4 product manufactured with AKTi revealed the AKTi-expanded T-cells had a greater proliferation or an enhanced memory phenotype; scRNASeq analyses are ongoing for the ADP-A2M4CD8 product.An increase in IL-12 levels (MSD) in serum post-infusion suggests that endogenous immune cells are being activated, further resulting in increased levels of IFN gamma (MSD) secretion relative to patients who received first-gen product. These enhanced products improve CD4+ T-cell killing, release more inflammatory cytokines, proliferate more robustly with an early memory phenotype, and better engage the patient‘s endogenous immune system when compared to first-gen products or next-gen manufactured without AKTi. Trial Registration NCT04044859

P2, N=45, Recruiting, Adaptimmune | Not yet recruiting --> Recruiting

P2, N=45, Not yet recruiting, Adaptimmune | Initiation date: Jun 2021 --> Sep 2021

No abstract available

P2, N=45, Ongoing, Adaptimmune LLC

Prior to infusion, pts receive lymphodepletion with fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days. ADP-A2M4CD8 SPEAR T-cells have shown an acceptable safety profile. Emerging efficacy data remain encouraging with the majority of pts experiencing disease control and RECIST responses in several solid tumor types. A full update will be presented at the conference.

P1, N=45, Recruiting, Adaptimmune | N=30 --> 45 | Trial completion date: Jan 2036 --> Apr 2037 | Trial primary completion date: Jan 2021 --> Apr 2022

P2, N=45, Not yet recruiting, Adaptimmune

Prior to infusion, pts receive lymphodepletion with fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days. Results As of 16 July 2020, 5 pts (1 with MRCLS, 2 with esophagogastric junction [EGJ] cancers, 1 with ovarian cancer, and 1 with head and neck cancer) were treated with ADP-A2M4 CD8 (range ~1 to 5.7 billion transduced cells)...Translational data and early clinical results indicate that co-expression of the CD8α co-receptor on CD4+ SPEAR T-cells may increase the potency of the product by conferring additional killing activity to the helper T-cell subset. This dose escalation trial is ongoing and updated clinical and translational data will be presented.

Prior to infusion, pts receive lymphodepletion with fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days. Results As of 16 July 2020, 5 pts (1 with MRCLS, 2 with esophagogastric junction [EGJ] cancers, 1 with ovarian cancer, and 1 with head and neck cancer) were treated with ADP-A2M4 CD8 (range ~1 to 5.7 billion transduced cells)...Translational data and early clinical results indicate that co-expression of the CD8α co-receptor on CD4+ SPEAR T-cells may increase the potency of the product by conferring additional killing activity to the helper T-cell subset. This dose escalation trial is ongoing and updated clinical and translational data will be presented.