On January 19, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium ("ASCO GI"), the Company presented a poster with study results for satricabtagene autoleucel ("satri-cel", R&D code: CT041, an autologous CAR-T product candidate against Claudin18.2), which include the dose escalation results of the Phase 1b ELIMYN18.2 study (Cohort A) in gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC) in the US (Press release, Carsgen Therapeutics, JAN 19, 2024, View Source [SID1234639373]).

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"The treatment options for advanced GC/GEJ or PC patients are limited. The data we presented at the 2024 ASCO (Free ASCO Whitepaper) GI of the Phase 1b ELIMYN18.2 study demonstrated encouraging safety and efficacy profile of satri-cel (CT041), a first-in-class CAR T-cell against Claudin18.2. We will continue to drive the global clinical development of satri-cel and look forward to sharing more data updates on satri-cel in the future." Raffaele Baffa, MD, PhD, Chief Medical Officer of CARsgen Therapeutics, remarked.

Poster #356: CLDN18.2 Chimeric Antigen Receptor T Cell Therapy for Patients with Advanced Gastric and Pancreatic Adenocarcinoma: Results of ELIMYN18.2 Phase 1b Clinical Trial

The single-arm, open-label, Phase 1b/2 study (NCT04404595) evaluated the safety and efficacy of satri-cel in patients with Claudin18.2-positive histologically confirmed advanced GC/GEJ or PC who had progressed or were intolerant of at least 2 prior lines (GC/GEJ) or 1 prior line (PC) of systemic therapy. The Phase 1b study consisted of a modified 3+3 dose escalation/de-escalation with 5 dose levels (DLs) to be tested. Patients received a preconditioning regimen of fludarabine, cyclophosphamide, and nab-paclitaxel, followed by 1-3 cycles of satri-cel.

Herein, the Company presented the updated results of safety and determination of the Recommended Phase 2 Dose (RP2D). DL3 (600×106 cells) was selected as RP2D and enrollment in Phase 2 is currently ongoing. Adverse Events (AEs) were graded per CTCAE Version 5.0 and CRS and ICANS were graded by ASTCT 2019 consensus criteria. Objective Response Rate (ORR) and Clinical Benefit Rate (CBR) were assessed per RECIST 1.1, and tumor response (CR or PR) was confirmed by an imaging scan after the initial response assessment. CBR is defined as the incidence of a best overall response of CR, PR, or SD≥180 days.

As of September 15, 2023, the median follow-up duration was 8.9 months (range:1.5-18.7 months). 19 patients were treated (7 GC/GEJ, 12 PC) across 3 DLs ranging from 250-600×106 cells: DL1: 250-300×106 (n=6), DL2: 375-400×106 (n=6), DL3: 600×106 (n=7). All patients received prior systemic therapy, among which 6 GC/GEJ (85.7%) and 7 PC (58.3%) patients received ≥ 3 lines of prior systemic treatment. Median number of prior systemic treatment lines of patients with GC/GEJ or PC were 4 (2,10) and 3 (1,5) respectively. Median number of metastatic organs of all patients was 2.0. All patients received at least one infusion and median number of infusions for all patients was 2.0 (1,3).

Safety

Overall, the safety profile of satri-cel was encouraging. No hemophagocytic lymphohistiocytosis (HLH), dose-limiting toxicities (DLTs), or treatment-related deaths were reported. The vast majority of CRS was Grade 1 with three Grade 2 events and two Grade 3 events. Apart from 1 patient who experienced Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), no other ICANS events of any grade were observed. All events resolved.

Efficacy

As of September 15, 2023, the median follow-up duration was 8.9 months (range:1.5 to 18.7 months). 1 patient with GC/GEJ in DL3 achieved a CR. The confirmed ORR in patients with GC/GEJ in all DLs was 42.9% (3/7). CBR in patients with GC/GEJ or PC in DL3 was 71.4% (5/7) and in patients with GC/GEJ in all DLs was 57.1% (4/7). The median progression-free survival (mPFS) and median duration of response (mDOR) was 5.7 months and 6.9 months respectively in patients with GC/GEJ in all DLs. In DL3, median overall survival (mOS) in patients with GC/GEJ or PC was 12.9 months. The mOS in patients with GC/GEJ or PC in all DLs was 8.9 months.

Conclusion

The safety profile of satri-cel, the first autologous Claudin18.2 CAR T cell therapy, was encouraging. Initial efficacy was promising in heavily pre-treated Claudin18.2-positive advanced GC/GEJ and PC population and consistent with earlier reports.

About Satri-cel

Satri-cel (CT041) is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be the first-in-class globally. Satri-cel targets the treatment of Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Trials in CARsgen include investigator-initiated trials (NCT03874897), a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by U.S. FDA for the treatment of advanced GC/GEJ with Claudin18.2-positive tumors in January 2022 and was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer in November 2021. Satri-cel received Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer.