BOSTON ― The University of Texas MD Anderson Cancer Center‘s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts. This special edition features upcoming presentations by MD Anderson researchers at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting, including immunotherapy advances in human papillomavirus (HPV)-positive head and neck cancers, microbiome signatures linked with specialized immune-cell clusters, and promising early activity from novel immunotherapy drugs in advanced melanoma and colorectal cancer.
Profiling T cells from HPV-positive head and neck cancers reveals new cell therapy targets (Abstract 374)
Although human papillomavirus (HPV)-related head and neck cancers are marked by a unique viral immunological target, immune checkpoint inhibitors are effective in only a minority of patients. Cell therapies directly targeting HPV proteins could be an effective alternative approach. To identify potential target antigens and related T cells, researchers led by Nils-Petter Rudqvist, Ph.D., analyzed T cell responses against HPV16 – a high-risk type of the virus – in three patients with HPV-16 positive oropharyngeal cancers. The team identified 16 unique T cell responses against distinct HPV16 antigens, including one associated with survival. The researchers now are translating these results into a novel cell therapy. Rudqvist will present the findings Nov. 10.
Combination immunotherapy and radiation therapy promising for HPV-related head and neck cancers (Abstract 568)
For patients with recurrent or metastatic head and neck cancer (HNC) marked by positive PD-L1 expression, anti-PD-1 checkpoint blockade improves survival over chemotherapy. Still, opportunities remain to optimize the use of immunotherapy in human papillomavirus (HPV)-related HNCs. In a Phase II trial led by Maura Gillison, M.D., Ph.D., researchers evaluated treatment with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before and in combination with volume- and dose-adapted intensity-modulated radiation therapy (IMRT) for patients with newly diagnosed HPV-positive HNC. Among evaluable patients, the combination achieved a complete response rate of 90% and a two-year progression-free survival rate of 86%. Additionally, histological analysis before the start of radiation therapy showed less than 10% of viable tumor remaining in 48% of patients, including 37% with no viable tumor left, and circulating HPV was cleared in 30% of patients. The findings suggest this approach merits further study as an effective treatment option for these patients. Gillison will present updated results Nov. 11.
Microbiome signatures linked with specialized immune-cell clusters in cancers treated with neoadjuvant immunotherapy (Abstract 590)
Despite promising results with immune checkpoint inhibitors, durable response remains a challenge in many cancers and novel biomarkers are needed to improve patient selection in future trials. In previous studies, MD Anderson researchers reported that exceptional immunotherapy responses are characterized by distinct gut microbiome profiles as well as the presence of specialized immune-cell clusters, called tertiary lymphoid structures (TLS), in the tumor. In a new study led by Manoj Chelvanambi, Ph.D., Christina Roland, M.D., Jennifer Wargo, M.D., and Tina Cascone, MD., Ph.D., researchers studied paired tumor and stool samples from patients treated with neoadjuvant immunotherapy in three distinct Phase II trials of melanoma, sarcoma and non-small cell lung cancer. They identified unifying features within the gut microbiome linked with TLS presence across multiple cancer types, including central taxa, pathway and network properties. Future studies will aim to validate and translate these findings into microbiome-based therapies to promote TLS formation and, ultimately, enhance immunotherapy responses. Chelvanambi will present the findings Nov. 11.
Novel immunotherapy combination boosts T cell infiltration in cold tumors (Abstract 657)
Checkpoint inhibitors have not been effective in patients with microsatellite-stable colorectal and pancreatic cancer, partly because of poor T cell infiltration. NT-17 (efineptakin alfa) is a long-acting form of interleukin-7 which can increase T cell infiltration when combined with pembrolizumab (anti-PD-1). In a Phase II study led by Aung Naing, M.D., researchers evaluated NT-17 plus pembrolizumab in patients with these cancers. Among 53 evaluable patients, the combination significantly increased T cell infiltration in pre- versus post-treatment biopsies. The overall response rate (ORR) was 9.4% based on iRECIST guidelines. For patients with liver metastases – common with these cancers and difficult to treat – the combination achieved a disease control rate (DCR) of 25.6%. In patients with metastases elsewhere, the treatment had a 28.6% ORR and 71.4% DCR. The findings suggest NT-17 can boost T cell infiltration and immunotherapy responses in immunologically cold tumors, warranting further evaluation. Naing will present updated trial results Nov. 11.
Targeting PVRIG checkpoint demonstrates early antitumor activity in advanced microsatellite-stable colorectal cancer (Abstract 659)
Current options for patients with advanced microsatellite-stable colorectal cancer (MSS-CRC) provide limited benefits, and most patients also have liver metastases that do not respond to available immune checkpoint inhibitors. In a new Phase I trial, Michael Overman, M.D., and colleagues evaluated the combination of nivolumab (anti-CTLA-4) and COM701, a novel checkpoint inhibitor targeting PVRIG, in patients with metastatic MSS-CRC. The treatment was well-tolerated with a favorable safety profile. In 22 evaluable patients, the combination achieved an overall response rate (ORR) of 9%, which is higher than typical responses with standard of care. An exploratory analysis also demonstrated encouraging early results in patients with liver metastases, including a 12% ORR and 29% disease control rate. Translational data indicate the combination led to potent immune activation in the tumor microenvironment, and further studies are planned for COM701 in this setting. Overman will present the findings Nov. 10.
CD40 agonist plus pembrolizumab achieves encouraging early results in metastatic melanoma (Abstract 782)
Checkpoint blockade can provide significant benefits to many patients with metastatic melanoma, but some tumors do not respond and others can develop resistance following an initial response. To explore new approaches for improving immunotherapy outcomes, Salah-Eddine Bentebibel, Ph.D., Adi Diab, M.D., and colleagues led a Phase I/II trial to evaluate the combination of pembrolizumab (anti-PD-1) with sotigalimab, a CD40 agonist antibody, in patients with metastatic melanoma not previously treated with checkpoint inhibitors. The combination achieved an overall response rate of 50% in distant lesions and a disease control rate of 67% in 30 evaluable patients. The treatment was well-tolerated, and correlative studies indicate that sotigalimab effectively engaged the CD40 pathway, leading to increased innate and adaptive immune activation that was correlated with clinical responses. The results are encouraging and merit further investigation in a large, randomized prospective study. Bentebibel will present the trial results Nov. 10.
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