Moderna’s mRNA-Based Cancer Vaccine Shows Encouraging Results in Phase 1 Trial

Since the discovery that proved that cancer’s survival in the body depends on immune suppression, several therapies have been developed to boost the immune system to fight and kill cancers. One of them is a personalized cancer vaccine. This type of vaccine is based on the antigenic profile of the patient’s own cancer cells. Such vaccines boost the immune system’s ability to recognize and destroy antigens and establish protective immunity against specific molecules expressed in cancers.

While peptide-based cancer vaccines are quite famous in the field, Moderna is working on a vaccine that would inject mRNA against a cancer antigen to trigger an immune response. This is very similar to what the company has developed for the coronavirus vaccine. But instead of injecting the mRNA against the spike protein, the mRNA designed for the cancer vaccine is against a specific cancer antigen.

mRNA-4157

The two cancer indications, which Moderna targets, are Head and Neck Squamous Carcinoma (HNSCC) and Microsatellite stable colorectal cancer (MSS-CRC). The vaccine, mRNA-4157, is currently being tested in the Phase 1 trials in pair with Merck’s Keytruda, a checkpoint therapy with the idea that the addition of cancer vaccine to checkpoint therapy can augment the immunotherapy response.

The company presented interim data from the Phase1 trial on November 11th at the Society for Immunotherapy of Cancer’s Annual Meeting (SITC 2020). The combo treatment appeared somewhat effective in shrinking tumors. While it showed a 50% response rate in HNSCC patients, it failed to hit the mark in MSS-CRC patients. When Keytruda was given alone to HNSCC patients, median progression-free survival (mPFS) of 2.0 months and overall response rate (ORR) of 14.6 % was observed. However, when the checkpoint treatment was combined with Moderna’s vaccine, mPFS of 9.8 months and ORR of 50% was obtained.

“The data are preliminary, and the sample size is small, but it is promising,” Dr. Bauman said in a statement. “A Phase I trial is about safety first and foremost, and we now know this treatment is safe and tolerable. But, we also have a strong signal to point us to further study this in head and neck cancer. That is why we are excited to expand this trial.”

Unique Design

Moderna’s investigational vaccine is quite different from vaccines that have been approved so far for cancer treatments. Its design is based on unique antigens identified in tumors by predictor algorithms. Once the antigens are identified, they are used to develop a set of genetic instructions that are loaded onto a single mRNA molecule, which is then injected into the body to teach immune cells such as T cells to identify and attack mutated cancer cells. The best part is that one mRNA can deliver instructions for 34 different cancer antigens to the immune cells, improving the chance of killing cancer furthermore.

Topping the efficacy data is the safety profile of the vaccine. According to the statement, the vaccine was generally well tolerable and adverse events were typically low grade and reversible.

“We are encouraged by these interim data from our personalized cancer vaccine program, which involves designing and manufacturing a unique vaccine for each patient based on their specific tumor,” said Stephen Hoge, M.D., President of Moderna. “This study demonstrates the ability of Moderna’s mRNA personalized cancer vaccine to elicit clinical activity when given in combination with pembrolizumab. I would also like to welcome Dr. Aanur to Moderna and look forward to working closely with him to continue building our oncology therapeutic area.”

By Ruchi Jhonsa, Ph.D.

Related Article: BioNTech to Test mRNA-Based Cancer Vaccine with Regeneron’s anti-PD1 Drug in Melanoma Patients

References

1. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-clinical-updates-personalized-cancer-vaccine

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Author

Ruchi Jhonsa