MD Anderson Research Highlights: ESMO 2021 Special Edition
Key presentations to focus on novel cell therapies, antibody-drug conjugates and neoadjuvant immunotherapy
MD Anderson News Release September 17, 2021
The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recent studies in basic, translational and clinical cancer research from MD Anderson experts. This special edition features oral presentations by MD Anderson researchers at the virtual European Society for Medical Oncology (ESMO) Congress 2021 on novel therapeutic approaches, including cell therapy for solid tumors, antibody drug conjugates targeting TROP2 and neoadjuvant pembrolizumab for advanced solid tumors with mismatch repair deficiencies.
In addition, Gabriel Hortobagyi, M.D., will present overall survival (OS) results from the Phase III MONALEESA-2 trial of ribociclib and/or endocrine therapy in postmenopausal patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. The late-breaking abstract (LBA-17) will be presented on Sunday, Sept. 19, at 6:30 a.m. CST.
Anti-TROP2 drug SKB264 demonstrates promising results for treating locally advanced or metastatic solid tumors (Abstract 514O)
SKB264, an antibody drug conjugate, is made of an antibody that targets the trophoblast cell-surface antigen 2 (TROP2), which drives cancer growth by promoting cell self-renewal, proliferation, invasion and survival. Because TROP2 is commonly overexpressed in various types of solid tumor cancers, including breast, cervix, kidney, lung and pancreatic cancers, it has become an emerging area of interest as a therapeutic target.
Study lead Jordi Rodon Ahnert, M.D., Ph.D., will present findings from a global, first-in-human trial testing the safety, tolerability, pharmacokinetics and antitumor activity of SKB264 as monotherapy in patients with unresectable solid tumors that either did not respond to or relapsed from standard treatment. The results showed that all 18 patients who were in enrolled in three dose levels of the trial reported treatment emergent adverse events (TEAEs), with the most common being grade 1-2 nausea (72.2%), decrease in white blood cell count (22.2%) and anemia (16.7%). The most common grade 3 or greater TEAEs were decreased neutrophil count (27.8%), decreased white blood cell count (22.2%) and anemia (16.7%), but all patients recovered after receiving corresponding treatment.
The therapy achieved partial responses in six patients, including two with triple negative breast cancer, two with ovarian cancer, one with HER2+ breast cancer and one with gastric adenocarcinoma. The drug had an overall response rate of 35.3% and disease control rate of 70.6%. While the dose escalation study is still ongoing, the data so far has demonstrated encouraging safety and antitumor activity.
New targeted therapy shows promise against refractory mesothelin-expressing solid tumors in dose escalation study (Abstract 959O)
Mesothelin is a cell-surface glycoprotein that is normally found on mesothelial cells lining the pleura, peritoneum and pericardium. However, overexpression of this glycoprotein has been detected in various human cancers – including malignant mesothelioma, ovarian cancer, cholangiocarcinoma and non-small cell lung cancer – making it a possible candidate for targeted therapy.
Gavocabtagene autoleucel (gavo-cel), an anti-mesothelin T cell receptor fusion construct (TRuC), is a novel cell therapy that is engineered to recognize and destroy cancer cells by harnessing the entire T cell receptor. Principal investigator David S. Hong, M.D., will present data from a Phase I/II dose escalation clinical trial evaluating the safety of gavo-cel either as a single agent or following a lymphodepletion chemotherapy regimen in patients with treatment-refractory mesothelin-expressing solid tumors.
The study enrolled 17 heavily pre-treated patients who had tumors that expressed mesothelin on at least 50% of viable cancer cells and did not respond to any FDA-approved options. The findings showed that the toxicity profile of gavo-cel was manageable up to the maximum tolerated dose of 5x108/m2. Of the evaluable 16 patients who were treated with gavo-cel, 15 achieved 5% to 75% regression of their target lesions. Four of six patients who were treated with gavo-cel following lymphodepletion experienced more than 50% reduction in their tumor size and achieved partial response, indicating that lymphodepletion was linked to higher peak expansion and greater tumor regression. The disease control rate was 81%, and overall response rate was 25% by independent review and 31% for those who received gavo-cel following lymphodepletion.
Researchers plan to continue studying gavo-cel to identify the highest dose with acceptable toxicity and to launch Phase II of the study, which will test the efficacy of gavo-cel as a single agent and in combination with checkpoint inhibitors across different tumor types.
Neoadjuvant immunotherapy shows potential for organ-sparing approach in certain patients (Abstract 1758O)
The immune checkpoint inhibitor pembrolizumab significantly improves clinical outcomes in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) solid tumors. These tumors contain defects in normal DNA repair processes, leading to an accumulation of genetic mutations and to production of mutant proteins, or neoantigens, that can be recognized as abnormal by the immune system.
Neoadjuvant, or presurgical, therapy has the potential to extend the benefits of immunotherapy earlier in the course of treatment and spare patients from surgical resection of affected organs. Kaysia Ludford, M.D., and colleagues will present data from a Phase II MD Anderson study evaluating the safety and efficacy of pembrolizumab in 35 patients with localized resectable or high-risk resectable MSI-H/dMMR solid tumors.
The therapy was well tolerated, with grade 3-4 side effects seen in three patients, including transaminitis, diarrhea and type 1 diabetes. At a median follow up of nine months, the overall response rate, as determined by imaging, was 75%, including eight complete responses and 16 partial responses. Seven patients had stable disease and one had progressive disease. Evaluation of response by luminal endoscopy reported a complete response rate of 55% and near complete response rate of 18%.
After completing 12 months of pembrolizumab, four patients elected not to have surgery and had no recurrences after a median follow-up of three months. An additional five patients stopped therapy before one year of treatment and experienced a clinical benefit, including one patient with stable disease and four with partial or complete response. Among 15 patients who chose to undergo surgery, 10 experienced a complete response. The findings suggest that neoadjuvant pembrolizumab is safe and well tolerated and that non-surgical management for localized MSI-H/dMMR tumors should be further investigated.
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