Satri-Cel Shows Some Disease Control in Gastric/Gastroesophageal and Pancreatic Cancer

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Dose level 3 showed the most efficacy and has been selected for the phase 2 portion of the trial.

Satricabtagene autoleucel (satri-cel; CT041; CARsgen) chimeric antigen receptor (CAR) T-cell therapy has shown some efficacy in patients with heavily pretreated CLDN18.2-positive advanced gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC) treated in cohort A of the phase 1b ELIMYN18.2 clinical trial (NCT04404595).1

Updated data from the trial were presented in a poster by Gregory P. Botta, MD, PhD, associate professor of medicine, University of California San Diego, at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers (GI) Symposium, held January 18-20, in San Francisco, California.

“Claudin 18.2 (CLDN18.2) is a tight junction protein normally expressed in gastric mucosa and several types of cancer. CLDN18.2 is considered a potential therapeutics target. Autologous CLDN18.2 CAR T cell satri-cel was developed to treat solid tumors,” Botta and colleagues wrote in their poster.1

The ELIMYN18.2 trial evaluated the safety and efficacy of satri-cel in patients with advanced GC/GEJ or PC whose disease had progressed or was unresponsive to at least 2 prior lines (GC/GEJ) or 1 prior line (PC) of systemic therapy. The study followed a modified 3+3 dose escalation/de-escalation scheme with 5 dose levels (DL). Participants received a preconditioning regimen of fludarabine, cyclophosphamide, and nab-paclitaxel before receiving 1-3 cycles of satri-cel.

READ MORE: Enabling Wider Antigen Selection With Logic-Gated CAR T-Cell Therapy for Solid Tumors

Study participants had a median age of 43.0 years (range, 33-65; GC/GEJ) and 63.5 years (range, 54-77; PC); 7 had GC/GEJ and 12 had PC. Most were white with at least 3 median lines of therapy (GC/GEJ, n = 6, 85.7%; PC, n = 7, 58.3%). Participants had a median of 4 (range, 2-10; GC/GEJ) and 7 (range, 1-5; PC) lines of treatment, and a median of 29.3 (range, 13.7-74.7; GC/GEJ) and 20.6 (range, 7.7-97.7; PC) months since diagnosis. Prior therapy included surgery, systemic therapy, and radiotherapy in both arms. Most patients with PC had an ECOG PS score of 0 andmost with GC/GEJ (n = 9; 75.0%) had an ECOG PS score of 1 (n = 6; 85.7%). Participants received a median of 2 infusions of satri-cel (range, 1-3).

Investigators found that the safety profile of satri-cel was manageable, although all patients had at least grade 3 treatment-emergent adverse events (AEs) and there were 4 serious TEAEs related to satri-cel. The related TEAEs of at least grade 3 were cytokine release syndrome, hypotension, increased liver enzymes, hypoxia, and increased lipase. There was 1 case of grade 1 immune effector cell-associated neurotoxicity syndrome.

Participants had a median follow-up of 8.9 months (range, 1.5-18.7) and were treated at DL1 (250-300x106, n = 6), DL2 (375-400x106, n = 6), or DL3 (600x206, n = 7). Objective response rate was 42.9% (n = 3) in GC/GEJ, 16.7% (n = 2) in PC, and 42.9% overall in DL3, which was selected as the recommended phase 2 dose (RP2D). There was 1 complete response (CR) in GC/GEJ in DL3, 2 partial responses (PRs) in GC/GEJ, and 2 PRs in PC in DL3. Clinical benefit rate (CBR) was 57.1% (n = 4) in GC/GEJ, 33.3% in PC (n = 4), and 71.4% in DL3. Median duration of response (DOR) was 6.9 months in GC/GEJ (range, 2.6-not estimable [ES]), 3.4 months (range, 3.0-NE) in PC, and 3.7 months (range, 3.0-NE) in DL3.

“Satri-cel’s, the first autologous CLDN18.2 CAR T cell therapy, safety profile was encouraging, with manageable treatment-related AEs. Initial efficacy was promising in heavily pretreated CLDN18.2-positive advanced GC/GEJ and PC population and consistent with earlier reports. DL3 (600x106 cells) was selected as RP2D and enrollment in phase 2 is currently ongoing,” Botta and colleagues concluded.1

Satri-cel is currently on clinical hold along with 2 other of CARsgen’s clinical stage CAR T-cell therapies, CT053, also known as zevorcabtagene autoleucel (zevor-cel), and CT071, over chemistry, manufacturing, and controls-related concerns that arose after an FDA inspection of the company’s manufacturing facility in Durham, North Carolina.2

REFERENCES
1. Botta GP, Kelly RJ, Jin Z, et al. CLDN18.2 chimeric antigen receptor T cell therapy for patients with advanced gastric and pancreatic adenocarcinoma: Results of ELIMYN18.2 phase 1b clinical trial. Presented at: 2024 ASCO GI; January 18-20; San Francisco, California. Abstract #356
2. Inside information announcement clinical hold in the U.S. due to CMC related questions. CARsgen. Letter.
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