$25 Million Awards Help Cancer Researchers Make Clinical Trial Inroads

By Clinical Leader staff

Develop therapeutics to target oncogenic drivers of solid tumors in children.

Decipher the T cell receptor cancer-recognition code.

Determine why the incidence of early-onset cancers in adults is rising globally.

Understand the mechanisms through which genetics, biology, and social determinants affect cancer risk and outcomes in diverse populations.

These are the four research areas that five teams selected by Cancer Grand Challenges will pursue over the next five years.

Now in its fourth round, Cancer Grand Challenges — a global research initiative cofounded by Cancer Research U.K. and the National Cancer Institute in the U.S. —  supports cancer research that aims to answer some of the field’s most dire questions and pertinent needs. It awards teams, often composed of academic and commercial researchers from across the globe, up to $25 million to pursue some of cancer’s toughest challenges.

“We set the toughest challenges in cancer. These can span the research spectrum. Most [teams] will have a discovery element because there's still so much we don't know about cancer and how it develops. Some challenges are more focused on prevention, others on understanding mechanism, and others are more translational. The opportunity that Cancer Grand Challenges provides is that often one team/program can span all of these areas to take a comprehensive approach to tackle the challenge,” explained Head of Research Gemma Balmer-Kemp.

Team KOODAC, one of two pursuing a cure for solid tumors in kids, includes in its research plans for preclinical studies necessary to enable biomarker-driven clinical trials and develop a framework to deliver a Phase 1 study, should a viable candidate arise. The other team, PROTECT, aims to move any viable candidates along the pipeline, with the intent to deliver at least one optimized protein degrader for its application in early-phase clinical trials.

Since its inception in 2015, Cancer Grand Challenges has fielded hundreds of applications and whittled its awards down to a little over a dozen recipients. Of those, at least two have had direct clinical impact, said Balmer-Kemp.

Balmer-Kemp recently reflected on some of the teams assembled over the past four challenges and easily recalls the success of an inaugural team, Team PRECISION. Funded in 2017, PRECISION, with researchers in the U.S., U.K., and the Netherlands, improved our understanding of features that can distinguish a non-lethal growth from a potentially lethal malignant growth, to inform the development of approaches to specifically detect the cancers that require intervention. PRECISION focused on ductal carcinoma in situ (DCIS). Many people with DCIS receive treatment, but their DCIS may have never developed into invasive cancer; thus, there is a burden of overtreatment. Ultimately, the team wanted to implement biology-based, tailor-made, de-escalating management strategies for people with harmless DCIS, without compromising the excellent outcomes presently achieved by treatment for people with potentially hazardous DCIS. As it turns out, researchers and physicians often don’t know the lethality of a given cancer, so they overtreat the patient, just in case, with much harsher therapies than may be required. According to the team’s lay summary, “In lung cancer, for example, X-ray scans can’t distinguish between spots where there is nothing to worry about or the early stages of an aggressive cancer that needs prompt treatment.”

“The PRECISION team ran in parallel to three randomized controlled trials, LORD, LORIS, and COMET, which were not funded by Cancer Grand Challenges, to test the safety of active surveillance for DCIS,” explained Balmer-Kemp. “ Interestingly, insights generated by the PRECISION team resulted in the LORD trial switching to a patient preference (from randomized) trial, with [around] 80% of patients opting for active surveillance.”

One of the successful endeavors from the 2022 round came from Team NexTGen. This team, with members across the U.S., U.K., and France, sought to answer two questions (among others): “Can we develop a deeper understanding of the biology of children’s solid tumors to identify the best approach to develop novel therapies that target their unique biological features?” and “Can immunotherapeutic approaches be developed which are effective in the pediatric solid tumor setting?” In doing so, the goal was to bring next-generation CAR T cell therapies to children with sarcomas and brain tumors. According to Balmer-Kemp, the NexTGen team proposed three clinical trials as part of their application, and these are due to open later this year. These are three innovative Phase 1 clinical trials testing different steps in the development of T cells: a highly customizable CAR region; an engineering component that blocks a treatment-inhibiting cytokine in the microenvironment; and two T cell platforms for engineering and two administration routes. The synergy between the clinical studies and the team’s basic and preclinical research will support the iterative refinement of the CAR T cells developed through the program. The team’s highly integrated approach will enable clinical observations to inform lab studies, whose findings will in turn be translated into novel preclinical and clinical studies.

Balmer-Kemp was careful to note that the identification of the research areas and ensuing research includes the input of patient advocates. The Cancer Grand Challenges Patient Advocacy Panel is consulted in all stages of cancer cure development, from providing a more intimate human contact for bench scientists to being involved in the research, including sharing real-world patient experience to help researchers understand symptoms and needs and identify therapies that affect quality of life.

For more information on awards and project status, visit Cancer Grand Challenges.

About The Expert:

Gemma Balmer-Kemp is Head of Research for Cancer Grand Challenges at Cancer Research UK. As head of research, she oversees all scientific aspects of Cancer Grand Challenges, including the research portfolio, and the Cancer Grand Challenges Scientific Committee, shaping and implementing future funding calls, evaluating progress and impact, and engaging and building deep relationships with the growing global Cancer Grand Challenges research community. Her team also works to deliver the Future Leaders strategy and thinks about how to enable collaborations between teams and how we stimulate research in challenging areas where we haven't yet funded a team.

Gemma has been at Cancer Research U.K. for 10 years and has worked across multiple different areas, from discovery research to CRUK's Centres and Institutes. Before then she completed her Ph.D. in developmental and stem cell biology at UCL, studying heart development, regeneration, and repair.