After years of broad and rapid growth, immuno-oncology (IO) clinical trials seem to be shifting from the traditional heavyweights to new directions, according to the latest update of the global IO Landscape Analysis published in Nature Reviews Drug Discovery by the Cancer Research Institute (CRI) Anna-Maria Kellen Clinical Accelerator.
“As the field of IO matures and works to develop therapies that will be effective for all cancer patients, it is obvious that scientific innovation continues to drive clinical discovery,” says CRI CEO and Director of Scientific Affairs Jill O’Donnell-Tormey, PhD.
Overall, while the number of new IO trials dropped for the first time since this analysis began in 2018, a record number of IO targets (195) are being investigated in clinical trials launched in 2022. Significant increases in new cell therapies, cancer vaccines, and other immunomodulators led to “healthy signs of innovation” that will hopefully lead to more cures for more patients.
This latest analysis examined 9,007 IO trials that began between 2018 and 2022 and observed a 2.86% decrease in new trials in 2022 compared to 2021, driven by a 6.4% decrease in phase 2 trials. Conversely, the number of phase 1 and phase 3 trials increased by 8.8% and 6.6%, respectively. Among all trials, there was a 10.3% decrease in those using PD-1/PD-L1 inhibitors, whereas other targets like CTLA-4, LAG-3, and CD3 T cell-engager increased 17.9%, 36.8%, and 13.3%, respectively.
Cell therapy clinical trials increased across the board, especially with more novel approaches. Trials with the most established cell therapy technique — CAR T cells — increased 5.6%, compared to increases of 24.2% for other T cell therapies, 7.7% for natural killer cell therapies, and 28.6% for therapies involving bacteria.
Immense investments were made in cell therapies for the treatment of solid cancers, which have proven elusive for current cell therapies. The hope is they can begin to approach the incredible effectiveness these treatments have achieved in blood cancers. In 2022, cell therapy trials in solid cancers accounted for 47% of all cell therapy trials, up 14.2% from the previous year.
The scope of IO-based therapies also expanded, with the number of therapeutic targets expanding from 146 in 2020, to 160 in 2021, to 195 targets now in 2022. IO modalities with significant growth in trials included cancer vaccines (17.4%) and non-T cell immunomodulators (9.2%). For the latter, there was a prominent shift — 10.4% compared to 2021 — away from antibody-based therapies. In contrast, trials with recombinant or fusion proteins, now the dominant modality among non-T cell immunomodulators, grew by 8% in 2022.
“The changes we observe in our latest analysis of the IO landscape are very exciting for the IO field. We see that interrogation of novel targets and mechanisms of action keeps growing and that newer therapeutic modalities are gaining ground to anti-PD1/PDL1 monoclonal antibodies,” says the Nature Reviews Drug Discovery article’s first author, Ana Rosa Sáez Ibáñez, PhD, research analyst for CRI’s Clinical Accelerator and Venture Fund. “These newer agents, such as T-cell engagers, bispecific antibodies, and cell therapies in the solid tumor space, hold huge potentials. The fact that we observe an increase in research utilizing these modalities is good news for cancer patients.” (PB/Newswise)
