Advances from immuno-oncology (IO) are changing the standard of care of many types of cancer, and the paradigm of cancer treatments and drug development is being rewritten on a regular basis. Moreover, an unprecedented number of new investigational agents and companies are entering the field of IO. As such, it has become challenging for oncology physicians conducting clinical trials, industry veterans developing IO drugs, and even regulators reviewing novel IO agents to keep track of the rapidly evolving landscape. To help the key stake holders in the field understand the latest IO landscape, we sought to present an unbiased, neutral, scientifically curated, and timely updated analysis of all the current IO agents in clinical development and the clinical trials testing these agents. We based our analyses on information collected from numerous trusted and publicly available sources. We have developed two databases. One database tracks 2004 IO agents (940 in clinical stage and 1064 in preclinical stage) against 303 targets, from 864 companies; the other tracks 3042 active clinical trials of these agents with a target enrollment of 577 076 patients. This report provides key analyses of these data. Furthermore, we will discuss a number of important and actionable trends in the current IO landscape: a large number of companies developing agents against the same IO targets; a rapid increase in the number of anti-PD-1/L1 combination studies, many of which are testing the same combinations and following inefficient patterns; and a significant increase in the number of small, investigator-initiated studies. For each of the findings, we speculate the causes and discuss a few initiatives that aim to address some of these challenges. Finally, by making these landscape analyses available, we aspire to inform the cancer community as they seek to strive for efficiencies and innovation while avoiding duplication.

The Methodology for the Development of Innovative Cancer Therapies Task Force considered aspects of the design and conduct of early studies of combinations of immunotherapy agents during their 2018 meeting. The Task Force defined the relevant data to justify combination clinical trials, which includes a robust hypothesis for the combination, pre-clinical data with evidence of efficacy and an understanding of the pharmacodynamics effects of each agent, and ideally evidence of single agent activity. Evaluation of pharmacodynamic biomarkers is critical in early phase combination trials, and should be incorporated into trial objectives and go/no-go decisions. The Task Force also identified the need to develop assessment tools and end-points that capture the unique patterns of tumour responses to immunotherapy, including pseudoprogression and hyperprogression. At least one additional tumour measurement before baseline, and an early CT scan (at 4 weeks for example) would help define the incidence of hyperprogression, although a common definition is needed. Finally, the Task Force highlighted substantial redundancy and inefficiency in the combination immunotherapy space, and recommended the adoption of innovative trial designs.

Aim: To report of severe chronic oral mucositis (OM) in two pembrolizumab-treated cancer patients. Materials & methods: A retrospective chart review was performed. Inclusion/exclusion criteria detected patients that developed OM during pembrolizumab immunotherapy. In addition, we searched the literature for nonlichenoid OM in immunotherapy-treated cancer patients. Results: Two male patients treated for anaplastic astrocytoma and lung adenocarcinoma were included. Extensive painful OM (grade 4) developed in both patients during the course of immunotherapy and the ulcerations remained >30 weeks (>16 weeks after stopping immunotherapy). Superficial mucocele appeared in one patient. In one patient, pain relief was achieved with photobiomodulation (low-level laser) therapy. Conclusion: OM induced by immunotherapy may be a major cause of suffering and eating difficulties. In most cases, the OM lasted for months even after the drug was stopped. There is a controversy regarding the beneficial effect of corticosteroids on OM in these patients.