New Glioblastoma Vaccine Proves Promising Results in Phase Ib Clinical Trial

Glioblastoma is the most aggressive type of primary brain cancer, with a prognosis of 11-15 months with standard treatment. The results of a Phase 1b clinical trial of a new experimental glioblastoma vaccine developed by Jefferson and Imvax show that the treatment was well tolerated by patients, as the recurrence of the tumor was slowed down and the patient survived longer.

The research was presented at an oral session of the annual meeting of the American Association for Cancer Research (AACR) on March 31 in Atlanta, Georgia.

The researchers treated 33 patients with newly diagnosed glioblastoma multiforme with the new cancer vaccine (IGV-001) in a Phase 1b prospective clinical trial and compared the findings to one group historical comparison of 35 patients treated with the same care in the same facility. Results showed that patients treated with the vaccine had improved progression-free survival and improved overall survival compared to the control group treated with the standard treatment.

"The response we're seeing in some patients is very encouraging," says David Andrews, MD, professor of neurosurgery at the Vickie Institute of Neuroscience & Jack Farber – Jefferson Health and co-founder, chief physician and chief executive officer. interim of Imvax. "We look forward to launching a Phase II trial later this year to confirm these Phase 1b results."

The vaccine is created from the tumor cells of the patient taken during the surgical removal of the primary brain tumor. The researchers first take the cancer cells, treat them with an antisense oligodeoxynucleotide (AS-ODN) against IGF-R1, a receptor that stimulates tumor growth and metastasis, and then load them with additional AS-ODN in broadcast rooms. Then, the dime-sized chambers and their contents are irradiated and implanted under the skin of the patient's abdomen.

"Due to the combined effects of antisense and IGF-1R irradiation, our evidence shows that chamber tumor cells release antigens that, together with the immunomodulatory AS-ODN, will diffuse out of the chamber into the patient's body and immune system against brain tumor cells, "says immunologist D. Craig Hooper, Ph.D., professor of cancer biology at Sidney Kimmel Cancer Center – Jefferson Health and co-founder and Scientific Director of Imvax.

A nationally renowned neurosurgeon treating patients with glioblastoma for decades, Dr. Andrews was frustrated with the low treatment options for glioblastoma. He was interested in the use of antisense molecules, which make glioblastoma cells more sensitive to conventional radiotherapy. However, preclinical experiments and early clinical study of the effect of implantation of diffusion chambers containing glioblastoma cells showed radiographic evidence of late removal of the tumor. This delay has suggested that a systemic, possibly immune, response might be at play. To better understand the observations, Dr. Andrews contacted Dr. Hooper, who has extensive experience in the study of immune regulation. and special expertise in neuroimmunity.

Over the last fifteen years, translational research conducted by Dr. Hooper and clinical studies by Dr. Andrews have refined the diffusion chamber badociation product used in the context of the research. current phase 1b test.

"This is an extremely important advance coming from the researchers at the Sidney Kimmel Cancer Center, and we are excited about the potential of this intervention and, as is the case for an NCI-designated Cancer Center, we are proud to have provided seed money for this bold new idea, "said Karen E. Knudsen, Ph.D., executive vice president of oncology services and business manager at Sidney Kimmel Cancer Center.

Phase 1b clinical trial builds on previous work showing that standard treatment of glioblastoma damages the immune system and suggests that the vaccine would be more effective in patients whose immune system had not been compromised by previous treatment . The Phase 1b trial included only patients scheduled for surgery prior to the start of adjuvant treatment to treatment standards.

The study included 33 patients between September 2015 and March 2018. The study participants were divided into four groups treated at different doses of vaccine, ranging from 10 chambers for 24 hours to the minimum dose at one. maximum of 20 rooms for 48 hours. Patients were followed for a median of 13 months (ranging from four to 39 months).

The results showed that patients who received the Imvax glioblastoma vaccine had longer progression-free survival and longer overall survival – two common measures of success in cancer treatment – than the control group. The researchers did not observe any adverse events related to the vaccine. The median prognosis, or overall survival, of patients treated with the highest dose of the vaccine was 21.9 months, compared with 14.6 months for standard treatment. The median progression-free survival was 10.4 months for the highest-dose vaccine, which is significantly higher than the 6.9 and 5.4-month studies published on the standard of care.

"It's a creative collaboration at its best.We have doctors facing the limits of medicine so they're reaching out to basic researchers to find potential solutions," said Robert Rosenwbader, MD, MBA , President and CEO of Vickie & Jack Farber. Institute of Neuroscience. "That's why university medical centers like Jefferson excel at innovations that improve lives." The depth of cellular and molecular knowledge in bench science drives the design of treatments that are most likely to succeed. basic laboratory science and clinical research combine pbadionate need to improve the lives of our patients and their families, we are developing tremendous progress in treatment paradigms. "

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