1. Samson, Kurt

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Results from a Phase I clinical trial suggest that administration of a neoantigen vaccine developed using a computational platform designed by researchers at Mt. Sinai Hospital in New York caused no serious safety concerns while demonstrating early signs of clinical utility in treating patients with different cancer types, researchers told the virtual AACR Annual Meeting 2021 (Abstract LB048).

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Administration of the neoantigen cancer vaccine, PGV-001, following standard-of-care adjuvant therapy was both well-tolerated and showed potential efficacy in patients with diverse tumor types with a high risk of recurrence, including lung and bladder diseases, 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.


"While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments," Marron told a pre-conference press briefing.

Thomas Marron, MD, P... - Click to enlarge in new windowThomas Marron, MD, PhD. Thomas Marron, MD, PhD

Although adoptive cell therapy relies on the engineering of immune cells to target cancer, cancer vaccines are a form of immunotherapy that indirectly attack cancer by training the patient's immune cells to recognize and destroy cancer cells.


And while the majority of investigational personalized cancer vaccines have been administered in the metastatic setting, accumulating evidence suggests that immunotherapies may be more effective if administered earlier, when patients have a smaller tumor burden, explained Marron.


"Cancer vaccines, which typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy," he said.


The researchers administered the personalized cancer vaccine after standard-of-care adjuvant therapy, when patients had minimal residual disease, might improve its efficacy.


Vaccine Research Details

To generate a personalized cancer vaccine, Marron and the team sequenced each patient's tumor and germline DNA and tumor RNA. They also identified each patient's HLA type (for human leukocyte antigen) to help predict the potential for immune recognition of identified neoantigens.


Using a computational pipeline developed at Mount Sinai called OpenVax, the researchers were able to 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 surgery and any standard-of-care adjuvant treatment, patients received 10 doses of the personalized vaccine over a 6-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 co-author Nina Bhardwaj, MD, PhD, Director of the Immunotherapy Program at The Tisch Cancer Institute, and the Ward-Coleman Chair in Cancer Research.


The vaccine also used 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 explained.

Nina Bhardwaj, MD, P... - Click to enlarge in new windowNina Bhardwaj, MD, PhD. Nina Bhardwaj, MD, PhD

Many Solid Tumor Types

In all, 15 patients were recruited for the study. The subjects enrolled to the trial had a range of malignancies, including non-small cell lung cancer, ductal or lobular breast cancer, head and neck cancer, ovarian or fallopian tube epithelial carcinoma, prostate cancer, urothelial cancer, renal cell carcinoma, and multiple myeloma, 13 of whom were vaccinated. Of the two patients who were not vaccinated, one with lung cancer experienced progressive disease while receiving adjuvant doublet chemotherapy, while the other patient, who was still in remission, selected a study that was closer to their residence. In total, 11 patients received all 10 vaccines, with the remaining two patients received seven and nine vaccines.


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 remained free of evidence of disease, four patients are receiving subsequent lines of therapy, four patients had 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.


Mt. Sinai has plans to open five other Phase I trials testing OpenVax with other therapies in cancers that include glioblastoma, bladder cancer, prostate cancer, and myeloproliferative neoplasms.


Limitations of the current study include its small size and its applicability given the diverse clinical population, tumor etiologies, and postoperative treatment courses, Bhardwaj noted.


Kurt Samson is a contributing writer.