T-cell activation and checkpoint suppression: triple immunotherapy to treat glioblastoma (GBM) 18-month survival rate of up to 50-70%!

Nov 22, 2020 // -- Inovio Pharma, a U.S. vaccine-cancer immunotherapy company, recently announced at the 2020 Annual Meeting of the Society of Neuro-Oncology the evaluation of T-cell-activated immunotherapy INO-5401 and code IL-12 that encode three tumor-related antigens (hTERT, WT1, and PSMA). Positive results from the newly diagnosed multi-form glioblastoma (GBM) Phase II clinical study (GBM-001, NCT03491683) of the PD-1 blockable antibody Libtayo (cemiplimab), developed in collaboration with immunoactivated agent INO-9012.
studies have shown that inO-5401-INO-9012 is toned and immunogenic in those with Libtayo, radiotherapy (RT) and TMZ, which can improve the median survival of newly diagnosed GBM patients.
survival data for the 18th month of this year show that 70% (14/20) of MGMT initiaters survived and 50% (16/32) of MGMT initiaters survived.
total survival (OS) was 17.9 months in patients with non-methylated GBM, which was more favourable than in the historical control group;
tested, most subjects showed a T-cell immune response to one or more tumor-related antigens encoded by INO-5401.
study, the immune response to all three tumor-related antigens was confirmed.
interim data show that (1) in the MGMT initiator non-methylation queue, so far, 19/22 (86%) patients have increased ifN-γ T-cell responses to one or more antigens encoded by INO-5401.
(2) In the MGMT initiator methylation queue, so far, 16/17 (94%) patients have increased their IFN-γ T-cell response to one or more antigens encoded by INO-5401 compared to baseline levels.
a new combination of INO-5401 plus INO-9012, it still has good tolerance for combined radiotherapy and TMZ and Libtayo.
data from the study will be available in the coming months, including relevant immunological and histological data, as well as studies of total drug exposure and accompanying medications.
glioblastoma (GBM, pictured: verywellhealth.com) is the most common and aggressive type of brain cancer and remains a devastating disease for patients and caregivers.
a limited number of new therapies have been approved in the past 10 years, the prognosmation is extremely poor.
total survival of patients receiving standard treatment was approximately 15 months, and the average progression-free lifetime was approximately 7 months.
the United States, the annual incidence of glioblastoma is estimated at 11,362, or 3.21 cases per 100,000 people, with a medium age of 65 at the time of diagnosis.
Ino-5401 code Inovio is used in combination with checkpoint inhibitors for SynCon® antigens for hTERT, WT1 and PSMA and is expected to be a powerful cancer immunotherapy.
National Cancer Institute has previously highlighted hTERT, WT1 and PSMA in a series of key cancer antigens as priorities for the development of cancer immunotherapy.
it is known that these three antigens are overexpressed and frequently mutated in a variety of human cancers, and targeting these antigens may be effective in treating cancer patients.
INO-9012 is a T-cell immunoactivation agent coded IL-12.
previously released non-human primate test data show that inO-5401 and INO-9012 combined drugs can produce a powerful T-cell immune response to hTERT, WT1, PSMA.
Libtayo (cemiplimab) is a tumor immunotherapy developed by Sanofi and Regenerative, an all-human monoclonal antibody for the immunosuppressor PD-1 (procedural cell death protein-1).
Libtayo belongs to PD-(L)1 tumor immunotherapy, a high-profile type of tumor immunotherapy designed to use the body's own immune system to fight cancer, by blocking the PD-1/PD-L1 signaling path pathrapies to kill cancer cells, with the potential to treat a variety of types of tumors. "This is a landmark joint trial in which a new DNA vaccine is combined with a checkpoint inhibitor and chemotherapy," said Dr. David Reardon, co-lead researcher of the
GBM-001 study and clinical director of the Neuro-Oncology Center at the Dana Faber Cancer Institute.
look forward to continuing to review these data to look at patients who are most likely to benefit from this innovative approach and see if the survival of these very difficult patients will be extended over time."
combination of the immune response with clinical results may prove insights.
" Dr Jeffrey Skolnik, Senior Vice President of Clinical Development at Inovio, said: "InO-5401-INO-9012, together with Libtayo and RT/TMZ, can produce cancer antigen-specific T cells that may be able to attack GBM and provide survival advantages.
We are using our immunology knowledge to define a patient population by continuing to evaluate all of our data: effectiveness, safety and, most importantly, immunogenicity and tissue expression data: in this patient group, this new combination of DNA drugs and checkpoint inhibitors may provide a survival advantage.
" () Original source: INOVIO Nows Clinical Results of its DNA Medicines INO-5401 and INO-9012 in Novel Combination with PD-1 Resor Libtayo? (cemiplimab) in the Treatment of Newly Diagnosed Glioblastoma Multiforme at Society for Neuro-Oncology 2020 Annual Meeting