Breakthrough Clinical Results
CARsgen Therapeutics announced positive results from a Phase II clinical trial (CT041-ST-01, NCT04581473) of satricabtagene autoleucel (satri-cel), a Claudin18.2-targeted CAR T-cell therapy, in patients with advanced gastric/gastroesophageal junction cancer (G/GEJC). The trial demonstrated a significant improvement in progression-free survival (PFS) and a clinically meaningful improvement in overall survival (OS) compared to the treatment of physician's choice (TPC). Satri-cel showed a manageable safety profile. These findings support satri-cel as a potential new standard of care for this patient population.
Key Highlights
- Significant improvement in progression-free survival (PFS) in patients receiving satri-cel compared to TPC.
- Clinically meaningful improvement in overall survival (OS) observed with satri-cel treatment.
- Favorable safety profile with manageable cytokine release syndrome (CRS).
- Satri-cel shows potential as a new standard of care for advanced G/GEJC.
Study Design Parameters
Key Trials for Gastric Cancer: Study Design Parameters and Endpoints
STOMACH Trial
This randomized, clinical multicenter trial compares open versus minimally invasive gastrectomy after chemotherapy for gastric cancer. The trial includes adult patients with primary carcinoma of the stomach that is surgically resectable (T1-3, N0-1, M0) after neo-adjuvant chemotherapy. The primary endpoint is quality of oncological resection, measured by radicality of surgery and number of retrieved lymph nodes. Secondary outcomes include patient-reported outcomes measures regarding quality of life, postoperative complications, and cost-effectiveness. The sample size is 168 patients based on a non-inferiority model for lymph node yield. The pathologist is blinded towards patient allocation.
Dutch Randomized Controlled Trial
This is a non-blinded, multicenter, prospectively randomized controlled superiority trial comparing laparoscopic and open gastrectomy for resectable gastric cancer. It includes patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and ECOG performance status 0-2. The sample size is 210 patients from ten Dutch centers. The primary outcome is postoperative hospital stay. Secondary outcomes include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life, and cost-effectiveness. The trial started December 2014 with a 3-year inclusion and 5-year follow-up.
FLOT Regimen Retrospective Study
This retrospective study evaluated the FLOT regimen in metastatic gastric cancer from January 2015 to December 2020. It included 94 HER-2 negative metastatic gastric cancer patients. Outcomes measured included median overall survival (13.5 months), progression-free survival (7 months), 1-year survival rate (53.6%), objective response rate (64.8%), and complete response (7.4%). Common grade 3-4 toxicities included neutropenia (44.6%), leukopenia (27.6%), neuropathy (12.7%), and fatigue (9.5%).
Complete Preoperative FLOT Chemotherapy Case Series
This study evaluated eight cycles of FLOT regimen before surgery. Of the 59 patients, 58 received preoperative cycles and 31 completed all eight cycles. Major adverse events occurred in 65.5% of patients. Outcomes included 18.2% pathologic complete response, 39.4% had no lymph node involvement, and overall survival was 21.32 months.
CRITICS-II Trial
This is a multicentre phase II non-comparative study of patients with clinical stage IB-IIIC resectable gastric adenocarcinoma. Patients are randomized between three treatment arms. The primary endpoint is event-free survival 1 year after randomization. Secondary endpoints include toxicity, surgical outcomes, percentage of radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers.
Total Neoadjuvant Therapy Trial
This prospective, multicenter, single-arm, phase II clinical trial for locally advanced gastric cancer explores total neoadjuvant therapy. The primary objective is to assess pathological complete response. Secondary objectives include toxicities, surgical complications, tumor downstaging rate, and R0 resection rate.
Recent Studies
Recent Studies for Gastric Cancer: Interventions and Outcomes
KEYNOTE-811 Study
This study evaluated SoC (standard-of-care) plus camrelizumab (PD-1 antibody) versus SoC alone for patients with HER2-positive advanced gastric cancer.
Efficacy outcomes: - Higher ORR (75.0% vs. 46.2%, P=0.032) - Higher DCR (96.4% vs. 69.2%, P=0.003) - Longer median OS (18.4 vs. 13.2 months, HR=0.343, 95% CI: 0.151-0.783, P=0.008) - Longer median PFS (3.78 vs. 1.74 months, HR=0.416, 95% CI: 0.186-0.932, P=0.027)
Safety outcomes: - Higher incidence of RCCEP, abnormal liver function, and hypothyroidism in the combination group
DESTINY-Gastric01 Trial
This open-label, randomized, phase 2 trial evaluated trastuzumab deruxtecan compared with chemotherapy in patients with HER2-positive advanced gastric cancer.
Intervention details: - Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor - Patients received trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy - 187 treated patients: 125 received trastuzumab deruxtecan and 62 received chemotherapy
Efficacy outcomes: - Objective response reported in 51% of patients in the trastuzumab deruxtecan group vs 14% in the physician's choice group (P<0.001) - Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median 12.5 vs 8.4 months) - Hazard ratio for death: 0.59 (95% confidence interval, 0.39 to 0.88; P=0.01)
Safety outcomes: - Most common adverse events of grade 3 or higher: decreased neutrophil count (51% vs 24%), anemia (38% vs 23%), and decreased white-cell count (21% vs 11%) - 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis - One drug-related death (due to pneumonia) in the trastuzumab deruxtecan group
S-1 Studies in Advanced Gastric Cancer
Two pivotal phase II studies demonstrated promising results for S-1 in advanced gastric cancer.
Efficacy outcomes: - High response rates of 44% and 49% - Overall survival time was 207 and 250 days respectively - Response rates comparable to combination chemotherapies like 5-FU plus CDDP - Advantages include being an oral drug with improved quality of life
Safety outcomes: - Adverse reactions occurred in 74.3% of patients, with 14.9% being grade 3 or worse - Main adverse reactions were myelosuppression and GI toxicities
Meta-analysis of ICIs plus Chemotherapy
This meta-analysis examined first-line immune checkpoint inhibitors (ICIs) plus chemotherapy compared to chemotherapy alone.
Efficacy outcomes: - Better OS (HR 0.76, 95% CI 0.72-0.81) - Better PFS (HR 0.68, 95% CI 0.61-0.75) - Higher ORR (RR 1.29, 95% CI 1.20-1.40) - Higher DCR (RR 1.06, 95% CI 1.03-1.09) - Significant OS benefit predictors included PDL-1 CPS ≥ 10, TPS ≥ 1%, and male gender
Safety outcomes: - Higher rates of adverse events in ICIs plus chemotherapy group, including immune-related AEs
Drug used in other indications
Based on the provided context, there is no information available about "satri-cel" being trialed for gastric cancer or any other indications. The context does not mention "satri-cel" at all, nor does it provide any details about clinical trials related to this treatment. No data is available regarding intervention models for satri-cel trials.