Personalized Cancer Vaccine for the Treatment of Solid Tumors

A clinical stage biotechnology company announced that it has started dosing patients in a Phase 1 study of mRNA-4157, an mRNA-based personalized cancer vaccine.

“An individualized medicine designed to help each patient’s immune system better recognize cancer as foreign and attack it would be a critical addition to oncologists’ treatment arsenal, potentially helping many more patients respond more effectively to treatment,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna. 

The Phase 1 open-label, dose escalation, multicenter study in the United States (KEYNOTE-603) will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with KEYTRUDA® (pembrolizumab), an anti-PD-1 therapy, in subjects with unresectable solid tumors.

KEYNOTE-603 is expected to enroll up to 90 patients across multiple clinical study sites in the United States. Part A of the study will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors (in the adjuvant setting).

Part B of this clinical study will evaluate mRNA-4157 in combination with Merck’s KEYTRUDA in subjects with unresectable solid tumors.

The first-in-human dosing of mRNA-4157 marks a key milestone in the strategic collaboration between Moderna and Merck to advance the novel mRNA-based personalized cancer vaccine in combination with KEYTRUDA for the treatment of multiple types of cancer.

“When we combine the potential for robust T-cell response stimulated by our mRNA vaccine, which encodes for 20 patient-specific mutations, with Merck’s checkpoint inhibitor, Keytruda, we have a unique opportunity to make a transformative difference for patients with cancer,” said Dr. Zaks.

Moderna is a clinical stage pioneer of messenger RNA (mRNA) therapeutics and vaccines, an entirely new drug technology that directs the body’s cells to produce intracellular or secreted proteins.

Roger M. Perlmutter, M.D., Ph.D., President, Merck Research Laboratories said “This trial leverages advances in genomics, advanced data analytics, and immunology to permit the generation of personalized cancer vaccines, a potentially transformative approach to cancer treatment.”

“Checkpoint inhibitors and other immuno-oncology therapies are continuing to revolutionize how we treat cancer. However, despite the strong and durable responses we see in some patients, many other patients’ disease continues to progress,” said Howard A. “Skip” Burris III, MD, President, Clinical Operations & Chief Medical Officer at Sarah Cannon, and a Principal Investigator of the mRNA-4157 Phase 1 study.

Using algorithms developed by its in-house bioinformatics team, Moderna predicts 20 neoepitopes present on the patient’s cancer that should elicit the strongest immune response, based on unique characteristics of the patient’s immune system and particular mutations.

Moderna then creates a vaccine that encodes for each of these mutations and loads them onto a single mRNA molecule.

Once injected into the patient, the vaccine should direct the patient’s cells to express the selected neoepitopes. In turn, this may help the patient’s immune system better recognize cancer cells as foreign and destroy them.

Moderna plans to manufacture and supply each individually manufactured personalized cancer vaccine to patients within weeks.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.