Key scientific highlights from the 31st Annual Meeting of the Society for Immunotherapy of Cancer

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Late-breaking data represent the most recent advances in cancer immunotherapy clinical trials

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With just one day left of the largest scientific conference dedicated exclusively to cancer immunotherapy, the meeting continues to gain momentum. The Society for Immunotherapy of Cancer (SITC) 31st Annual Meeting & Associated Programs held November 9-13, in National Harbor, MD has attracted nearly 2,800 multidisciplinary experts from academia, industry, and government to discuss the latest advances in cancer immunology and immunotherapy.

Late-breaking clinical trials presented at SITC 2016 have a particularly significant impact on the field due to the robust and innovative nature of the data. One presentation that garnered attention was a phase III trial of pembrolizumab (anti-PD-1 therapy) versus investigators’ choice of standard chemotherapy agents for the treatment of advanced urothelial (bladder) carcinoma that progressed or recurred following prior therapy. The trial was halted following an interim analysis, due to the markedly superior response in the cohort of patients treated with pembrolizumab. Presented by Joaquim Bellmut, MD, PhD (Dana-Farber/Brigham and Women’s Cancer Center), this international study of 542 patients from 29 countries reported significantly longer overall survival in patients treated with pembrolizumab, which was also associated with fewer side effects compared to chemotherapy. In contrast to similar trials, patient eligibility was not dependent on pre-treatment PD-L1 expression. This trial supports the role of pembrolizumab in second-line treatment of patients with advanced bladder cancer whose disease has progressed despite platinum-based chemotherapy.

Following the approval of nivolumab (anti-PD-1) in combination with ipilimumab (anti-CTLA-4) in advanced melanoma, the CheckMate 032 study seeks to expand the use of this combination therapy into additional types of cancer. Padmanee Sharma, MD, PhD (University of Texas MD Anderson Cancer Center) presented the first interim data of two different dose schedules of nivolumab and ipilimumab (1mg/3mg [N1I3] vs. 3mg/1mg [N3I1]) or nivolumab alone (3mg/kg [N3}) , in a phase I/II trial in patients with advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy. Although enrollment is ongoing and longer follow-up is needed, preliminary results of the combination strategy demonstrated an objective response rate of 38.5%, 26.0% and 25.6% in the N1I3, N3I1 and N3 arms, respectively. Additionally, side effects reported for the combination treatment groups were similar to what has been seen in other studies.

Continuing on the theme of immune checkpoint inhibition, Rom Leidner, MD (Earle A. Chiles Research Institute) presented preliminary efficacy data from an early phase study of a first-in-class antibody, lirilumab. Lirilumab functions as a checkpoint inhibitor for natural killer (NK) cells, which play a critical role in innate immunity. Following recent reports that combining lirilumab with nivolumab demonstrated no added toxicity over nivolumab alone, this study investigated lirilumab plus nivolumab in patients with squamous cell carcinoma of the head and neck that progressed after prior therapy. Of the evaluable patients thus far, 7/29 (24%) had an objective response (OR) per RECIST v1.1 criteria, and target tumor lesion size decreased by >80% in five patients. The responses appeared durable as the median duration of response has not yet been reached. The investigators assessed PD-L1 biomarker expression in tumor samples and, Dr. Leidner commented that “objective responses in the combination arm are tracking in lockstep with increasing PD-L1 expression”.

The search for additional immune checkpoints, driven by the need to increase the number of patients who respond to treatment, has also yielded a novel member of the B7/CD28 checkpoint family, PVRIG. John Hunter, PhD (Compugen Inc.) described how a novel computational algorithm was used to characterize this new immune checkpoint, which is a member of the TIGIT family of interacting molecules. PVRIG is expressed on T cells and NK cells and has potential to stimulate both innate and adaptive immunity. Using a PVRIG-Fc fusion construct, activation of CD4+ and CD8+ T cells were observed in vitro. The combination of anti-PVRIG and anti-PD-L1 was shown to inhibit tumor growth and increase survival in preclinical models of both CT26 and MC38 murine colorectal cancer.

ABOUT SITC
Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a non-profit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, healthcare professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC, our educational offerings and other resources at sitcancer.org and follow us on Twitter, LinkedIn, Facebook and YouTube.
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Erin Irelan
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