Immuno-oncology (IO) agents have transformed the oncology landscape in the last decade, particularly immune checkpoint inhibitors (ICIs) in solid tumor settings and chimeric antigen receptor (CAR) T-cells in hematological malignancies, with patients who previously had very limited therapeutic options achieving long term remissions and even cure. Continued investment into IO R&D in both academia and industry will further improve the clinical outlook of oncology patients, says GlobalData.
GlobalData’s latest report, “Thematic Research: Immuno-Oncology” explores the IO pipeline and identifies over 700 novel agents currently in clinical development. Cell therapies are ahead of other IO classes, with more than 300 agents in clinical development in the 8MMs, of which the majority are CAR-T cell therapies. Checkpoint modulators follow cell therapies with over 140 agents in clinical development.
Avigayil Chalk, Senior Oncology and Hematology Analyst at GlobalData, comments, “The greatest investment is in classes of agents with demonstrated efficacy, namely, cell therapies and ICIs. However, pipeline ICIs are facing extreme competition as they enter a heavily crowded treatment landscape, with multiple ICIs having regulatory approval across lines of therapy in a broad range of solid tumor indications. Targeting of a novel checkpoint that improves response rates or enables retreatment of checkpoint-exposed patients are strategies, which may give novel agents a share of this market.”
Chalk adds, “Pipeline cell therapies entering the hematological malignancy landscape will also have to tackle fierce competition, with multiple cell therapies already marketed for the easier-to-target B-cell malignancies. Cell therapies that may successfully compete in the B-cell malignancy setting include those that target novel or multiple receptors/antigens, those with simplified or shortened manufacturing processes, and those that are allogeneic. Cell therapies, including CAR-Ts, CAR-Natural Killer cells (CAR-NK), and stimulated dendritic cells for solid tumor indications are also in development, however, with a lack of suitable targets, and minimal demonstrated efficacy, this is a high-risk, high-reward approach.”
Multi-specific antibodies, of which the majority are bispecific T-cell engagers (BiTEs) are another IO class that holds very significant potential, with over 100 such agents in the clinical development phase. There are currently four marketed BiTEs, three of which have gained regulatory approval for hematological malignancies and one for uveal melanoma.
Chalk continues, “There is great enthusiasm amongst physicians for the wider application of BiTEs, which could become a significant class in both the hematological and solid tumor settings. BiTEs link endogenous effector T-cells to tumor-expressed antigens, thereby promoting an anti-tumor immune response. Unlike CAR-T therapies, BiTEs are an “off-the-shelf” product, giving them a significantly simplified manufacturing process, a lower cost, and increased availability to a greater patient population across markets.”
Therapeutic cancer vaccines are a class of IO agents that have historically shown disappointing clinical efficacy, however, in recent years, there has been an increase in the number of such agents in clinical development, particularly those based on mRNA technology.
Chalk adds, “Educating a person’s immune system to target rapidly evolving, genetically complex tumors, which still present self-antigens, is a tremendous challenge.”
However, if an immune response is successfully generated, persisting antibodies and memory cells could provide long-term immunity, thereby preventing disease relapse. Last year, Moderna’s mRNA-4157/V940 provided the first demonstration of efficacy for this therapeutic class, generating much excitement in the oncology field.
Chalk concludes, “Despite the advances in IO, there are still significant unmet needs in oncology, with the majority of patients diagnosed with advanced disease not achieving long-term remission. The exciting and novel IO pipeline is set to address some of this unmet need, improving the outlook for patients.”