On January 29, 2025 ImmunityBio, Inc. (NASDAQ: IBRX) reported it has entered into a collaboration and supply agreement with BeiGene, Ltd. (to be changed to BeOne Medicines, Ltd.), a global oncology company, to conduct a confirmatory randomized Phase 3 clinical trial (ResQ201A-NSCLC), combining BeiGene’s tislelizumab, a PD-1 checkpoint inhibitor (CPI), and ImmunityBio’s ANKTIVA (nogapendekin alfa inbakicept-pmln) (Press release, ImmunityBio, JAN 29, 2025, View Source [SID1234649924]). The Phase 3 ResQ201A-NSCLC study (NCT06745908) aims to confirm the efficacy and safety of combination ANKTIVA plus CPI therapy previously demonstrated in the trial QUILT 3.055 and provide evidence of the potential for these two immunotherapeutic agents to improve overall survival in patients with advanced or metastatic NSCLC who have acquired resistance to immune CPI therapy.
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The Phase 3 trial design is based on the synergistic potential already demonstrated in the QUILT 3.055 study that a CPI and ANKTIVA, an IL-15 superagonist, prolongs overall survival (OS) in the study population compared to historical controls in this setting. In Phase 1 and 2 studies, ANKTIVA has demonstrated the capability of rescuing T cells, and thus CPI efficacy, through the molecule’s unique mechanism of action. ANKTIVA is the first FDA approved molecule that has demonstrated the ability to increase lymphocytes via its proliferative IL-15 stimulatory action. ANKTIVA stimulates the proliferation of natural killer cells and CD4+ and CD8+ T cells, which in turn restores MHC-1 presentation, allowing T cells to regain their cytotoxic activity, and thereby rescue CPI activity.
Multiple Phase 1 and 2 studies have demonstrated prolonged overall survival with this combination approach, in comparison to historical results with chemotherapy in this patient population. 1,2 In these multi-site trials, the combination of ANKTIVA plus the CPI, with no intervening therapy when the patient progressed on the CPI, demonstrated a median OS (mOS) of 17.1 months (95% CI: 4.6, NR) in patients with PD-L1 ≥ 50% and a mOS of 19.6 months (95% CI: 6.2, NR) in patients who relapsed on checkpoint inhibitor. QUILT 3.055 confirmed these findings with a mOS of 14.1 months (95% CI: 11.7, 16.3), as presented at World Lung on Oct 2024.3, 4
The mechanism of the rescue of NSCLC patients who had failed checkpoint inhibitors is through the MOA of ANKTIVA in which NK cells and T cells are proliferated with rescue of lymphocytes and MHC-I. Proliferation of lymphocytes has been observed In healthy volunteers, and is due to the unique mechanism of ANKTIVA as an IL-15 agonist as described on the package insert. 5,6 On the basis of these findings, ImmunityBio intends to file a BLA for ANKTIVA + checkpoint inhibitor in second / third line NSCLC patients who have progressed on CPI therapy.
ImmunityBio will conduct this confirmatory Phase 3 trial globally across multiple sites; when fully enrolled, it is expected to include 462 participants.
"The challenge oncologists face in the next five years is how to manage the many patients who do not respond to CPI therapy after an initial response," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "Currently, options are limited for these second- and third-line patients with NSCLC whose cancer continues to progress on CPIs. The finding that these ‘cold’ tumors, which have evaded T cells, can now be rendered ‘hot’ through the activation of natural killer cells with ANKTIVA, is exciting. To our knowledge, ANKTIVA is the first approved cytokine to address low white cell count (lymphopenia), which occurs following chemo-immunotherapy and radiotherapy. On the basis of ANKTIVA’s mechanism of action of proliferating T cells as well as NK cells, ANKTIVA has the potential to serve as the foundational cytokine to address loss of activity in the multiple tumors in which CPIs are approved."
According to the American Cancer Society, lung cancer is the second most common cancer in the U.S. In 2025, it is estimated that 226,650 new cases of lung cancer will be diagnosed in the U.S. and 124,730 deaths will be attributed to the disease. NSCLC accounts for about 87% of all lung cancer diagnoses, and there are very few successful treatment options for these patients once the cancer spreads beyond the lungs.
"ImmunityBio and BeiGene share a similar vision to advance the next generation of oncology immunotherapies to address unmet needs. We are excited to explore the potential of our PD-1 inhibitor, tislelizumab, in combination with ANKTIVA," said John V. Oyler, Co-Founder, Chairman and CEO of BeiGene. "I’ve admired Dr. Soon-Shiong’s bold approach to medicine and look forward to working with him and his team as the ResQ201A-NSCLC study gets underway. Together, we hope to help metastatic lung cancer patients who may have few options left."
The primary endpoint of the study is overall survival, with secondary endpoints including disease control rate, progression-free survival, objective response rate and safety.
For more information about the trial, please visit www.Immunitybio.com.
About ANKTIVA
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.
ANKTIVA was approved by the FDA in 2024 for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors. For more information, visit ImmunityBio.com (Founder’s Vision) and Anktiva.com.