ImmunityBio, Inc. (NASDAQ: IBRX) has announced a strategic collaboration and supply agreement with BeiGene, Ltd. (soon to be renamed BeOne Medicines, Ltd.), a global oncology company. The partnership will focus on conducting a confirmatory, randomized Phase 3 clinical trial (ResQ201A-NSCLC), investigating the combination of BeiGene’s tislelizumab, a PD-1 checkpoint inhibitor (CPI), and ImmunityBio’s ANKTIVA® (nogapendekin alfa inbakicept-pmln). The ResQ201A-NSCLC study (NCT06745908) aims to validate the safety and efficacy of this combination therapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have developed resistance to immune checkpoint inhibitors.
A Novel Approach to Overcoming CPI Resistance
The Phase 3 trial builds upon findings from the QUILT 3.055 study, which demonstrated the synergistic potential of CPIs and ANKTIVA—an IL-15 superagonist—in prolonging overall survival (OS) among NSCLC patients. ANKTIVA has shown the ability to reinvigorate T cells and restore CPI efficacy through its novel mechanism of action. As the first FDA-approved molecule capable of increasing lymphocytes via its IL-15-mediated stimulatory effect, ANKTIVA promotes the proliferation of natural killer (NK) cells and CD4+ and CD8+ T cells. This restoration of major histocompatibility complex class I (MHC-I) presentation enables T cells to recover their cytotoxic capabilities, thereby revitalizing CPI effectiveness.
Multiple Phase 1 and Phase 2 studies have demonstrated significant OS benefits using this approach. In these trials, the combination of ANKTIVA with a CPI, without any intervening therapy after CPI progression, yielded a median OS (mOS) of 17.1 months (95% CI: 4.6, NR) in patients with PD-L1 ≥ 50% and 19.6 months (95% CI: 6.2, NR) in those who relapsed on a checkpoint inhibitor. The QUILT 3.055 study confirmed these results, reporting a mOS of 14.1 months (95% CI: 11.7, 16.3) as presented at the 2024 World Lung Conference.
The Science Behind ANKTIVA’s Potential
Checkpoint inhibitor failure remains a major hurdle in NSCLC treatment, necessitating novel approaches to immune system activation. The proposed mechanism of action for ANKTIVA in rescuing CPI-resistant NSCLC patients is its ability to proliferate NK cells and T cells, restoring lymphocyte function and MHC-I presentation. Clinical trials in healthy volunteers have confirmed ANKTIVA’s ability to stimulate lymphocyte proliferation, attributed to its IL-15 agonist properties.
Based on these compelling findings, ImmunityBio plans to submit a Biologics License Application (BLA) for ANKTIVA in combination with a checkpoint inhibitor for second- and third-line NSCLC patients who have experienced disease progression despite CPI therapy.
Confirmatory Phase 3 Trial Details
The ResQ201A-NSCLC trial, led by ImmunityBio, will be conducted at multiple sites worldwide and is expected to enroll 462 patients upon full recruitment. The study aims to confirm the clinical benefits observed in previous trials and potentially establish ANKTIVA as a foundational cytokine therapy for patients who have exhausted standard treatment options.
Dr. Patrick Soon-Shiong, Founder, Executive Chairman, and Global Chief Scientific and Medical Officer of ImmunityBio, emphasized the urgency of developing solutions for NSCLC patients who no longer respond to CPI therapy. “The challenge oncologists face in the next five years is managing the increasing number of patients who initially respond to CPIs but then progress.
Currently, these patients have very limited options. ANKTIVA’s ability to convert ‘cold’ tumors into ‘hot’ tumors by activating NK cells is a game-changing approach. To our knowledge, ANKTIVA is the first approved cytokine to address lymphopenia, a common side effect following chemo-immunotherapy and radiotherapy. Its ability to stimulate both NK cells and T cells positions it as a potentially foundational cytokine therapy for many CPI-resistant cancers.”
According to the American Cancer Society, lung cancer remains the second most common cancer in the U.S., with an estimated 226,650 new cases and 124,730 deaths projected in 2025. NSCLC accounts for 87% of lung cancer diagnoses, and treatment options are often limited for patients with metastatic disease.
BeiGene Co-Founder, Chairman, and CEO John V. Oyler echoed ImmunityBio’s enthusiasm for the partnership. “ImmunityBio and BeiGene share a vision to advance the next generation of oncology immunotherapies to meet critical unmet needs. We are excited to explore the potential of our PD-1 inhibitor, tislelizumab, in combination with ANKTIVA. I have long admired Dr. Soon-Shiong’s innovative approach to medicine, and we look forward to working together to advance the ResQ201A-NSCLC study and improve outcomes for metastatic lung cancer patients.”
Study Endpoints and Future Outlook
The primary endpoint of the Phase 3 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, visit www.ImmunityBio.com.
About ANKTIVA®
ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex that mimics the natural biological properties of IL-15 receptor alpha. By binding to IL-15 receptors on NK, CD4+, and CD8+ T cells, ANKTIVA enhances the immune response against cancer cells. The drug has demonstrated superior pharmacokinetic properties, prolonged persistence in lymphoid tissues, and improved anti-tumor activity compared to native IL-15.
ANKTIVA was FDA-approved in 2024 for treating BCG-unresponsive non-muscle invasive bladder cancer carcinoma in situ (CIS) with or without papillary tumors. For more information, visit ImmunityBio.com and Anktiva.com.
About ImmunityBio
ImmunityBio is a vertically integrated biotechnology company dedicated to developing next-generation therapies and vaccines that enhance the body’s natural immune response against cancers and infectious diseases. Its immunotherapy and cell therapy platforms aim to create durable and safe treatments that reduce reliance on high-dose chemotherapy. Designated an FDA Breakthrough Therapy, ANKTIVA is the first FDA-approved immunotherapy for non-muscle invasive bladder cancer CIS that activates NK cells, T cells, and memory T cells for a long-duration response.
For more information, visit ImmunityBio.com and follow the company on LinkedIn, Twitter (X), Facebook, and Instagram.
About BeiGene
BeiGene, soon to be renamed BeOne Medicines Ltd., is a global oncology company dedicated to developing innovative and accessible cancer treatments. With a growing pipeline of novel therapeutics, BeiGene is committed to accelerating drug development through internal innovation and strategic collaborations.
To learn more, visit www.beigene.com and follow the company on LinkedIn, Twitter (X), Facebook, and Instagram.
