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Personalized Cancer Vaccine Given After Adjuvant Therapy Safe, Shows Early Efficacy in Multiple Tumor Types

PHILADELPHIA – Treatment with the neoantigen cancer vaccine PGV-001 following standard-of-care adjuvant therapy was well tolerated and showed potential clinical benefit in patients with diverse tumor types with high risk of recurrence, according to results from a phase I clinical trial presented during Week 1 of the virtual AACR Annual Meeting 2021, held April 10-15.

“While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments,” said study author Thomas Marron, MD, PhD, assistant director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and assistant professor of medicine (hematology and medical oncology) at the Icahn School of Medicine at Mount Sinai in New York. “Cancer vaccines, which typically combine tumor-specific neoantigens with an adjuvant that primes the immune system, may be a viable treatment strategy for patients without a pre-existing antitumor response.”

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have a smaller tumor burden,” said study author Nina Bhardwaj, MD, PhD director of the Immunotherapy Program at The Tisch Cancer Institute, and the Ward-Coleman Chair in Cancer Research at the Icahn School of Medicine at Mount Sinai. “We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, when patients have minimal (typically microscopic) residual disease.”

To generate a personalized cancer vaccine, Marron and colleagues sequence each patient’s tumor and germline DNA and tumor RNA. They also identify the patient’s HLA (for human leukocyte antigen) type to help predict the potential for immune recognition of identified neoantigens. Using a computational pipeline developed at Mount Sinai called OpenVax, the researchers can identify and prioritize immunogenic neoantigens to synthesize and incorporate into the vaccine. Up to 10 neoantigen peptides, specific to the patient’s HLA type, were included in each patient’s personalized vaccine, Marron said.

Following their surgery and any standard-of-care adjuvant treatment, patients received 10 doses of the personalized vaccine over a six-month period, which was given with the immunostimulant poly-ICLC. “Poly-ICLC is a synthetic, stabilized, double-stranded RNA viral mimic capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing de novo immune responses against tumor neoantigens,” explained Bhardwaj. The vaccine also uses a tetanus helper peptide. Because most people have been vaccinated against tetanus, this helper peptide further activates the immune response against the co-administered neoantigens, she said.

A total of 15 patients were enrolled in the trial and had vaccine successfully synthesized. All patients had received curative-intent surgery (for solid tumors) or autologous stem-cell transplant (for multiple myeloma) and statistically had at least a 30 percent chance of disease recurrence. Two patients never received the vaccine (one due to disease progression and one because the patient opted for an alternative clinical trial). Among the 13 patients who received the PGV-001 vaccine, 10 had solid tumor

diagnoses and three had multiple myeloma. All patients received at least seven doses of vaccine, and 11 patients received all doses of the vaccine.

After a mean follow-up of 925 days, four patients remain without evidence of disease, four patients are receiving subsequent lines of therapy, four patients have died, and one patient was lost to follow-up. The median progression-free survival from time of surgery or transplant was 618 days. The vaccine was well tolerated, with roughly one-third of patients developing grade 1 injection-site reactions. Among the patients without evidence of disease, diagnoses include myeloma, lung, breast, and urothelial cancer.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” said Marron.

Limitations of this study include its small size and its applicability given the diverse clinical population, tumor etiologies, and post-operative treatment courses, Bhardwaj noted.

This study was sponsored by the Parker Institute for Cancer Immunotherapy and the Tisch Cancer Institute.

Marron has served on advisory and/or data-safety monitoring boards for Regeneron, Genentech, Boehringer Ingelheim, AstraZeneca, Atara, and Celldex, and he receives research support from Regeneron, Bristol Myers Squibb, and Boehringer Ingelheim.

Bhardwaj is an extramural member of the Parker Institute for Cancer Immunotherapy; receives research funds from Regeneron, Harbour Biomed, and Dragonfly Therapeutics; and is on the advisory boards of Neon Therapeutics, Novartis, Avidea, Boehringer Ingelheim, Rome Therapeutics, Roswell Park Comprehensive Cancer Center, BreakBio, Carisma Therapeutics, CureVac, GenoTwin, BioNTech, Gilead and Tempest Therapeutics, and the Cancer Research Institute.