Moderna's mRNA-4359 cancer vaccine is showing early promise in treating solid tumors, according to interim data from a Phase I/II trial. The first-in-human study, involving 19 patients with advanced melanoma, lung cancer, and other solid tumors, suggests the vaccine can stimulate the body's immune system to recognize and fight cancer cells.
The trial, a dose escalation study, administered between one and nine doses of mRNA-4359 to patients. Researchers observed that in eight of the 16 evaluable patients, tumors did not grow, and no new tumors appeared. Importantly, the treatment was reported to be well-tolerated, with no serious side effects observed.
Dr. Debashis Sarker, UK chief investigator and consultant in medical oncology at Guy’s & St Thomas’ NHS Foundation Trust, presented the findings at the European Society of Medical Oncology conference in Barcelona. He stated, "This study evaluating an mRNA cancer immunotherapy is an important first step in hopefully developing a new treatment for patients with advanced cancers. We have shown that the therapy is well tolerated without serious side effects and can stimulate the body’s immune system in a way that could help to treat cancer more effectively."
The mRNA-4359 vaccine utilizes mRNA technology, similar to that used in COVID-19 vaccines, to teach the immune system how cancer cells differ from healthy cells, mobilizing it to destroy them. The vaccine is designed to activate the immune system to recognize two proteins of interest, PD-L1 and IDO1, triggering a response of immune cells to kill cancer cells and reducing other immune cells that can prevent the immune system from fighting cancer.
Ongoing and Future Studies
The study is currently enrolling patients with specific cancers, including melanoma and non-small-cell lung cancer, to receive low doses of mRNA-4359 in combination with pembrolizumab (Keytruda). This part of the trial will include sites in the UK, USA, Spain, and Australia, marking a significant international effort.
Kyle Holen, senior vice president and head of development, therapeutics and oncology at Moderna, noted, "We are encouraged by the phase 1 results of mRNA-4359, which demonstrate its potential to elicit strong antigen-specific T-cell responses while maintaining a manageable safety profile. This novel approach could be a key component in shifting the tumour microenvironment toward a more immune-permissive state, offering potential hope for patients with advanced solid tumours."
Context within Cancer Vaccine Development
The mRNA-4359 trial is part of a broader wave of research exploring mRNA vaccines for cancer treatment. Moderna and Merck are also collaborating on a Phase III trial of a personalized mRNA vaccine for melanoma, mRNA-4157 (V940), in combination with Keytruda. BioNTech is also conducting trials of its vaccine BNT116 for patients with non-small cell lung cancer (NSCLC).
While these early results are promising, researchers emphasize the need for caution due to the small sample size and the primary focus on safety and dose determination in this phase of the trial. Further studies are essential to fully evaluate the efficacy of mRNA-4359 and its potential to improve outcomes for patients with advanced cancers.
