Here are some highlights of clinical trials presented at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting by researchers from The University of Texas MD Anderson Cancer Center. They include breakthroughs in cancer care, updates in clinical research, and efforts in cancer prevention.
First-in-Human Trial of Gastric Cancer Therapy
Some patients with gastric cancer and other solid tumors have abnormal expression of Claudin18.2, a protein found in gastric epithelial cells, making it a potential therapeutic target. In a phase I trial, Dumbrava et al examined the safety and efficacy of TAC01-CLDN18.2, a new treatment using T-cell antigen coupler technology to modify a patient’s T cells, so the T cells naturally recognize and attack the cancer cells of the individual patient. The trial enrolled heavily pretreated patients with various cancer types expressing Claudin18.2. In the first two cohorts, no dose-limiting toxicities were reported, and disease control was observed in five of six initial patients eligible for assessment (83%). These results, including an ongoing confirmed partial response in the first cohort, suggest that TAC01-CLDN18.2 is safe and shows clinical activity, leading to further treatment of cohort three.1
COVID mRNA Vaccines and Immune Checkpoint Inhibition
Earlier results have suggested that COVID-19 mRNA vaccines may enhance immunotherapy and improve survival by increasing PD-L1 expression. Patients with non–small cell lung cancer who were vaccinated within 100 days of their biopsies and treated with immune checkpoint inhibitors lived twice as long as those who were unvaccinated. Patients with metastatic melanoma also had better outcomes with vaccination, including improved survival and lower risk of disease progression. Updated results from the study reported by Grippin et al demonstrated that COVID-19 mRNA vaccines stimulate secretion of interferon alpha (IFN-⍺), which further enhances responses to immune checkpoint inhibitors. Healthy volunteers had a significant increase in plasma IFN-⍺ levels 24 hours after vaccination compared with baseline. These results provide further insights into the underlying mechanisms behind the improved outcomes of vaccinated patients treated with immunotherapy.2
Mortality Risk in Patients With Immune Checkpoint Therapy–Related Myocarditis
Myocarditis related to immune checkpoint therapy is associated with a reported mortality rate of up to 50%. Neuromuscular immune-related adverse events, such as myositis and myasthenia gravis, often occur simultaneously with immune checkpoint therapy–related myocarditis and can affect the diaphragm. In a recent study, Ostos-Mendoza et al reported that diaphragm failure may be a major driver of mortality related to immune checkpoint therapy–related myocarditis. In 103 patients who experienced immune checkpoint therapy–related myocarditis, the all-cause mortality rate was 51.4%, with 30.2% of deaths attributed to myocarditis related to immune checkpoint inhibitor treatment. Deaths related to diaphragm failure and immune checkpoint inhibitor–related myocarditis occurred more frequently in those patients with concurrent myositis and/or myasthenia gravis than in those with isolated myocarditis related to immune checkpoint therapy. The findings suggest that neuromuscular toxicities and diaphragm failure are major contributors to the high mortality rates associated with immune checkpoint inhibitor–related myocarditis, underscoring a need for better strategies to manage these significant side effects.3
AI-Assessed Tumor Microenvironment May Inform Outcomes in Rare Tumors
Rare tumors are difficult to study because of a lack of available data and models, but artificial intelligence (AI) may help to generate computational models that may predict treatment response. Derbala et al used an AI-powered analysis of biopsies from 84 patients with 10 different histologic subtypes of rare tumors to characterize tumor responses and changes in the tumor microenvironment before and during treatment with the PD-1 inhibitor pembrolizumab. Changes in tumor-infiltrating lymphocyte density and tumor content were significantly associated with progression-free and overall survival, especially in subgroups with a higher density of tumor-infiltrating lymphocytes. The researchers reported that this AI-powered assessment may potentially inform future personalized treatment strategies and perhaps better predict responses in immunotherapy trials for patients with rare tumors.4
Tumor Immune Microenvironment in Pleural Mesothelioma
Pleural mesothelioma is an aggressive cancer in lung tissue associated with asbestos and is poorly understood with limited treatment options. A deeper understanding of the tumor immune microenvironment may help to identify potential targets for new therapeutic strategies. Therefore, Tomczak et al used multiomics analysis to examine the tumor immune microenvironment in tumor samples from 26 patients with pleural mesothelioma who underwent surgical resection. The study characterized the immune-genomic landscape of the tumor immune microenvironment, highlighting the tumor-infiltrating lymphocytes and, in some immunosuppressive tumors, the presence of hyperexpanded T-cell receptor clones with a potential antitumor response. The findings provided further insights into the tumor immune microenvironment of pleural mesothelioma and define distinct immune features to inform future clinical trial design.5
All SITC content from MD Anderson can be found at MDAnderson.org/SITC.
DISCLOSURE: For full disclosures of all study authors, visit SITCCancer.org.
REFERENCES
1. Dumbrava EE, Iqbal S, Turcotte S, et al: A phase 1/2 study evaluating the safety and efficacy of autologous TAC T cells in subjects with claudin 18.2+ advanced solid tumors. 2024 SITC Annual Meeting. Abstract 1472. Presented November 8, 2024.
2. Grippin A, Copling S, Kim A, et al: SARS–COV-2 mRNA vaccines are associated with type I interferon signaling and improved clinical responses to immune checkpoint inhibition. 2024 SITC Annual Meeting. Abstract 1037. Presented November 8, 2024.
3. Ostos-Mendoza KC, Chen L, Lopez-Rodriguez A, et al: Neuromuscular immune-related adverse events and diaphragmatic insufficiency as mortality predictors in immune checkpoint therapy associated myocarditis. 2024 SITC Annual Meeting. Abstract 1190. Presented November 8, 2024.
4. Derbala MH, McGonagle KE, Batral H, et al: Artificial intelligence-powered assessment of tumor microenvironment in pre-treatment and on-treatment biopsies informs treatment outcomes to pembrolizumab in patients with rare tumors. 2024 SITC Annual Meeting. Abstract 1207. Presented November 8, 2024.
5. Tomczak K, Lermi NO, Deboever N, et al: An integrated tumor, immune and genetic landscape of pleural mesothelioma to unleash effective immunotherapy avenues. 2024 SITC Annual Meeting. Abstract 1413. Presented November 8, 2024.
