Phase 1 oncology trials increased in number and heterogeneity between 2009 and 2021, with a particular increase in multi-agent combination and immunotherapy trials.

An Australian-led study published in Contemporary Clinical Trials Communications [link here] analysed global trends from 7,061 phase 1 trials in adults with solid cancers identified via clinicaltrials.gov.

The study found phase 1 trials increased by a mean of 5.2 % per year between 2009 and 2021, with the most rapid increase of 27.5 % from 2015 to 2016.

“Of note, there has been a significant increase in the proportion of Ph1 clinical trials which included an Asia-Pacific site, from a mean of 30.1 % (2009–2014) to 41.8 % (2015–2020) (p=0.003),” it said.

Multi-agent combination trials were consistently more frequent than single-agent trials, while single-class trials were consistently more frequent than multimodal combination trials.

Chemotherapy trials declined by an average of 0.8 % annually, while immunotherapy agents increased at a mean annual rate of 22.8%, and immunotherapy plus targeted combinations rose by 41.1 %.

“The Food and Drug Association (FDA) approved the use of the CTLA-4 inhibitor ipilimumab for melanoma in March of 2011, but it was not until 2014, when the PD-1 inhibitor pembrolizumab was approved, that rates of immunotherapy use in Ph1 trials increased dramatically,” the investigators said.

Trials of cellular therapies increased by about 15.5 % annually.

The study, led by senior investigator Associate Professor Ben Tran from the Peter MacCallum Cancer Centre and the Walter and Eliza Institute, also noted the impact of the COVID-19 pandemic on clinical trial activity.

“Trial numbers in Asia-Pacific and Europe were lower than expected by 21.0 % (415 v 328 trials) and 31.0 % (203 vs 140 trials) respectively,” they said.

“Marked shifts away from multi-regional collaboration were seen, increasing single-region trials in North America, while single-region trials registered in other regions remained steady.”

“This may impact negatively on the capacity for recruitment of large patient populations, reduce ethnic diversity in trial populations and limit capacity to study rare tumours or specific molecular subtypes.”

“More research is required to examine the permanence of Covid-19 pandemic related changes, and track the emergence of less common therapeutic classes, including ADCs, cellular and viral therapies.”