On August 6, 2024 Immunotherapy company ImmunityBio, Inc. (NASDAQ: IBRX), reported the opening of a clinical trial to study ANKTIVA (nogapendekin alfa inbakicept-pmln) together with the investigational AdHER2DC vaccine (autologous dendritic cells transduced with HER2 expressing adenovirus), in individuals with HER2-expressing endometrial cancer (Press release, ImmunityBio, AUG 6, 2024, View Source [SID1234645422]). It marks the latest trial involving ANKTIVA, the company’s IL-15 superagonist immune enhancer, to evaluate ANKTIVA as an agent to replace the short-term activity of checkpoint inhibitor immunotherapies with long-term effectiveness. ANKTIVA was recently approved by the FDA for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors.
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This Phase 1/2 QUILT 502 trial (NCT06253494) sponsored by the National Cancer Institute, part of the National Institutes of Health, will study whether the AdHER2DC vaccine in combination with ANKTIVA, pembrolizumab (checkpoint inhibitor), and lenvatinib (kinase inhibitor) can be safely administered in combination and provide preliminary clinical efficacy before a larger, more definitive study.
Endometrial cancer is the most common gynecological cancer in the U.S., and affects more than 65,000 women each year with incidence peaking around 50-60 years of age. The 5-year overall survival rate in patients with metastasis is around 20 percent; treatment options after the second-line treatment are limited.
The AdHER2DC vaccine targets the HER2 protein, which is elevated in 30% of patients with endometrial cancer and in more than 50% of high risk subtypes. The AdHER2DCs are autologous, using each participant’s own blood cells obtained through apheresis, a "loop" where blood is removed from one vein, passed through a machine to filter out target cells and then returned to the patient through another vein. The AdHER2DC is a proprietary agent of the NCI and it will be manufactured at the NIH Clinical Center for each study participant. The single agent AdHER2DC demonstrated safety profile and immunogenicity in a phase 1 clinical trial conducted by the NCI. The first treatment cycle is 28 days and each cycle after that will be 21 days. All participants will receive the vaccine and the two FDA approved drugs pembrolizumab and lenvatinib, and some participants will receive ANKTIVA.
Phase 1 of the open-label, two-arm Phase 1/2 study will determine recommended dose of pembrolizumab, lenvatinib, ANKTIVA and AdHER2DC in participants with HER2 positive endometrial cancer. The Phase 2 portion of the study will assess the efficacy of the combination of pembrolizumab, lenvatinib, ANKTIVA and the AdHER2DC vaccine in qualified participants as determined by the proportion of participants without disease progression at six months. The study will enroll 60 subjects and is expected to be completed in 2026.
"We are pleased to partner with the NCI on this important cancer control study involving ANKTIVA, which has demonstrated in clinical trials that activation of memory T cells may help deliver long-duration response well beyond that of checkpoint inhibitors alone," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We are hopeful that the AdHER2DC investigational vaccine plus ANKTIVA will ‘rescue’ the checkpoint inhibitor pembrolizumab and kinase inhibitor lenvatinib and lead to an improved response compared with the current standard of care in this high risk population."
ImmunityBio is already partnered with the NCI to study the use of ANKTIVA in cases of Lynch syndrome, a genetic condition that is linked with significantly increased incidence of cancers, particularly colon cancer. These studies along with the recent approval of ANKTIVA for bladder cancer signal the advent of the era of cytokines as the next-generation of immunotherapies.
To learn more about this study, please visit View Source
For patients interested in enrolling in this study, please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the website: View Source and/or [email protected].
The AdHER2DC vaccine is investigational. Safety and efficacy of this investigational agent have not been established by any health authority, including the FDA.
How ANKTIVA Works
The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response.
ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo.