Getting personal with mRNA cancer vaccines

BRIEFING

September 7, 2023

Daniel Knecht, MD, MBA

Vice President & Chief Clinical Innovation Officer, CVS Caremark

Messenger RNA, or mRNA, technology used to create the Moderna and Pfizer COVID-19 vaccines has been in development since the 1960s.https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer Now, seven decades later, the longstanding promise of using this technology to treat cancer is no longer just a possibility – it’s a reality.

There will be 1.9 million new cases of cancer and 609,820 deaths in the United States in 2023.https://seer.cancer.gov/statfacts/html/common.html

Cancer is the second leading cause of death in the United States.https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm But breakthroughs in oncology treatments can increase survival rates and decrease disease progression, helping patients lead longer, better lives.

Gaps with current cancer therapies

The main ways to treat cancer include chemotherapy, radiation therapy, stem cell or bone marrow transplant, surgery, and immunotherapy. These treatment types can be used alone or together.

Each cancer treatment has advantages and disadvantages.https://doi.org/10.1177/20503121211034366 While surgery is the most effective in the management of localized, early malignancies, it may not be as effective in later stages. Radiation and chemotherapy run the risk of damaging healthy tissue, in addition to other harmful side effects.

What are cancer vaccines and how do they work?

Therapeutic cancer vaccines treat existing cancer and stop it from growing or spreading. Because each person’s cancer is unique, many cancer vaccines are personalized to spot specific mutations in the patient’s cancer genome and teach the immune system how to recognize and destroy those specific mutated cancer cells.https://www.youtube.com/watch?v=wmnSXUqgi5Y The mRNA technology targets proteins (or antigens) not typically found on normal cells, which helps the immune system target only cancer cells and ignore healthy ones.https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer

So far, no mRNA cancer vaccines have been approved for use either alone or with other cancer treatments.https://www.youtube.com/watch?v=wmnSXUqgi5Y

A growing pipeline of mRNA cancer vaccines

Important research and clinical trials are underway to explore mRNA vaccines for different cancers such as melanoma, liver, prostate, ovarian, pancreatic, colorectal, and other advanced solid tumors. At least 13 clinical trials registered on ClinicalTrials.gov involve mRNA cancer vaccines.

BNT112 (BioNTech): Prostate Cancer

This multipronged vaccine targets 5 antigens that appear in prostate cancer.https://clinicaltrials.gov/study/NCT04382898

Phase 1/2 trial: The first patient enrolled in December 2019. Since then, patients have received BNT112 as a monotherapy or in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab).
What’s next: As of February 2023, enrollment is complete for those with metastatic castration-resistant prostate cancer and the clinical trial will only recruit patients with high-risk, localized prostate cancer.

BNT122 (BioNTech): Pancreatic cancer

Researchers at Memorial Sloan Kettering Cancer Center (MSK), BioNTech, and Genentech have developed a personalized mRNA vaccine against pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

Phase 1 trial: All patients received an immune checkpoint inhibitor before vaccination, and each vaccine targeted up to 20 neoantigens.https://www.nih.gov/news-events/nih-research-matters/mrna-vaccine-treat-pancreatic-cancer Findings show BNT122 (also referred to as autogene cevumeran) may have prevented or delayed recurrence of pancreatic cancers in about half of the 16 MSK patients who received it.https://investors.biontech.de/news-releases/news-release-details/positive-phase-1-data-mrna-based-individualized-neoantigenhttps://www.nature.com/articles/s41586-023-06063-y
What’s next: A new clinical trial is examining whether the vaccine reduces the risk of relapse after the tumor is removed by surgery.https://clinicaltrials.gov/ct2/show/study/NCT04161755 In addition to pancreatic cancer, BNT122 is in Phase 2 studies for melanoma in combination with Keytruda (pembrolizumab) and for colorectal cancer.

GRANITE (Gritstone Bio): Advanced solid tumors

This individualized vaccine program uses adenoviral vectors followed by a boost of self-amplifying mRNA – RNA that makes copies of itself – to deliver neoantigens.https://ir.gritstonebio.com/news-releases/news-release-details/gritstone-announces-updated-overall-survival-results-granite

Phase 1/2 study: Enrolled patients had previously treated, metastatic solid tumors. The vaccine demonstrated extended overall survival in multiple end-stage colorectal cancer patients, with no dose-limiting toxicities.https://www.nature.com/articles/s41591-022-01937-6
What’s next: A randomized, controlled Phase 2/3 trial is exploring the vaccine’s use in earlier disease settings.

mRNA-4157 (Moderna): Melanoma

This personalized mRNA cancer vaccine may trigger an immune response to up to 34 patient-specific tumor neoantigens.https://www.merck.com/news/moderna-and-merck-announce-mrna-4157-v940-in-combination-with-keytruda-pembrolizumab-demonstrated-a-statistically-significant-and-clinically-meaningful-improvement-in-distant-metastasis-free/

Phase 2 trial: Updated results of a randomized study found the mRNA vaccine in combination with Merck’s immune checkpoint inhibitor Keytruda (pembrolizumab) reduced the risk of death or recurrence of melanoma by 65 percent compared with Keytruda alone. The clinical benefit was similar for tumors with high and low mutation rates.
What’s next: The vaccine-Keytruda combination therapy has moved into Phase 3 development for the adjuvant treatment of patients with high-risk stage II-IV melanoma following complete resection. Also, mRNA-4157 is in Phase 1 studies for solid tumors and head and neck cancer. Moderna may seek faster regulatory approval for this personalized mRNA cancer vaccine.https://www.merck.com/news/merck-and-moderna-initiate-phase-3-study-evaluating-v940-mrna-4157-in-combination-with-keytruda-pembrolizumab-for-adjuvant-treatment-of-patients-with-resected-high-riskstage-iib-iv-melanom/

Challenges ahead for mRNA cancer vaccines

Preliminary research shows these customized therapies offer benefits in terms of survival and quality of life. But there are important steps to take to make mRNA cancer vaccines more accessible to more patients. These include:

Decreasing production times and improving ease of administrationhttps://dailynews.ascopubs.org/do/mrna-vaccines-promising-new-tool-fight-against-cancer-here-s-they-stand
Addressing relative instability and the potential for easy degradationhttps://dailynews.ascopubs.org/do/mrna-vaccines-promising-new-tool-fight-against-cancer-here-s-they-stand
Finding the right neoantigen candidates with DNA sequencinghttps://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer
Addressing the cost of personalized therapies, which can’t be produced in bulkhttps://scrubsmag.com/cancer-vaccines-could-soon-become-a-reality/
Figuring out the optimal combination of mRNA vaccines and available cancer therapieshttps://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer

Even with these challenges, the industry remains optimistic about mRNA vaccine technology and its role in fighting cancer.

This document contains references to brand-name prescription drugs that are trademarks or registered trademarks of pharmaceutical manufacturers not affiliated with CVS Health.

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Gaps with current cancer therapies

What are cancer vaccines and how do they work?