In this interview with Bobby Reddy, Chief Medical Officer at ImmunityBio, we explore the company’s groundbreaking work in cancer immunotherapy. The discussion focuses on the FDA’s RMAT designation for ANKTIVA and CAR-NK cells, the validation of biomarkers, and the ethical considerations of expanded access policies. Reddy shares insights into the scientific and commercial strategies that drive ImmunityBio’s mission to transform cancer treatment.
Moe: The FDA’s RMAT designation for ANKTIVA and CAR-NK cells relies on ALC as a biomarker. How confident are you that ALC-survival correlations will hold in real-world settings?
Bobby Reddy: It’s a central question for us. Historically, lymphocytes were important but lacked actionable treatments. With ANKTIVA, we can increase lymphocyte counts, which should be beneficial. Our Phase 2 pancreatic trial showed promising results, and we expect similar outcomes in future studies. The RMAT designation suggests that improving lymphocyte counts could lead to accelerated approvals, ultimately proving their value in extending survival. This approach leverages an existing biomarker, making it easier to integrate into current clinical workflows. We’re not introducing a new concept but enhancing an established one, which is routinely tested and understood in the medical community. This familiarity aids in its acceptance and application in real-world settings, ensuring that our interventions are both practical and impactful.
Moe: ANKTIVA activates NK, CD4+, CD8+ and memory T cells without upregulating Tregs. Can you provide evidence that this mechanism occurs consistently in human tumors?
Bobby Reddy: Our data is primarily human-based. We’ve published studies showing increased cell populations post-ANKTIVA in healthy volunteers and cancer patients. For instance, in combination with rituximab, we’ve observed increased lymphocyte counts, despite rituximab’s B-cell-killing properties. These findings, published in peer-reviewed journals, support our claims, although we acknowledge the need for further tumor-specific data. The studies by Rubenstein et al. and Foltz, published in Clinical Cancer Research, highlight these effects, demonstrating the potential of ANKTIVA to enhance immune cell proliferation in real-world settings. While we focus on peripheral blood data, the assumption is that these cells are also active in tumors. This is a critical area for further research, but the existing evidence provides a strong foundation for our approach.
Moe: You plan to file an Expanded Access Policy soon. How do you ensure this access isn’t seen as a revenue strategy bypassing rigorous data thresholds?
Bobby Reddy: We have ongoing rigorous trials, such as the Phase 3 trial in non-small cell lung cancer, involving 462 patients. These trials aim to meet global regulatory standards. The expanded access policy enables us to gather more comprehensive safety and efficacy data, informing future decisions while maintaining a focus on rigorous scientific validation. It’s about parallel processes—ensuring patient access while continuing to build a robust evidence base through comprehensive clinical trials. This dual approach ensures that while we provide access to those in need, we also adhere to the highest standards of scientific rigor. Our commitment is to both immediate patient needs and long-term validation of our therapies.
Moe: ANKTIVA and CAR-NK therapy may be effective across multiple tumor types. How do you reconcile this with the heterogeneity of the tumor microenvironment?
Bobby Reddy: It’s crucial to demonstrate real clinical benefit, which is why our trials focus on overall survival in difficult-to-treat diseases. We aim to meet global regulatory standards and drive clinical conviction. While we are optimistic, we remain grounded in the need for robust evidence to support the broad applicability of our therapies. The diversity of tumor microenvironments necessitates a nuanced approach, and our trials are designed to address these complexities by focusing on hard endpoints, such as overall survival. This ensures that our therapies are not only broadly applicable but also specifically effective in diverse clinical scenarios. Our strategy is to strike a balance between ambition and scientific rigor, ensuring that our claims are supported by robust evidence.
Moe: Combining ANKTIVA with PD-L1-targeted CAR-NK cells assumes synergy. Have you encountered paradoxical responses or resistance mechanisms in patients?
Bobby Reddy: Resistance mechanisms are complex and varied. While we don’t see 100% cures, the side effect profile of our therapies allows for potential combinations with other treatments. We are exploring these avenues, acknowledging that resistance patterns are diverse and require ongoing investigation. The absence of significant toxicity, such as cytokine release syndrome, makes ANKTIVA a promising candidate for combination therapies, which could potentially enhance its efficacy in overcoming resistance. This flexibility in combination strategies is a key advantage, allowing us to tailor treatments to individual patient needs and resistance profiles. Our ongoing research aims to understand further and address these challenges, ensuring optimal patient outcomes.
Moe: RMAT expedites approval with accelerated endpoints. What’s your long-term strategy for proving durable, clinically meaningful benefits post-launch?
Bobby Reddy: Following approval, we focus on collecting real-world data and implementing registry programs to demonstrate clinical and economic value. Our approved products already show durability, and we aim to expand labels and indications, ensuring long-term benefits are proven and recognized. The bladder program, for instance, highlights our commitment to demonstrating sustained efficacy and value, both clinically and economically. By continuously monitoring and analyzing real-world outcomes, we ensure that our therapies deliver on their promises over the long term. This commitment to ongoing evaluation and improvement is central to our strategy, ensuring that we not only meet initial expectations but exceed them.
Moe: ImmunityBio’s founder sees ANKTIVA as a paradigm shift. How do you ensure this science doesn’t outpace commercial feasibility, given the complexity and cost?
Bobby Reddy: For ANKTIVA, manufacturing at scale is feasible, and we’re developing in-house capabilities. Cell therapy is more complex, but our off-the-shelf approach and existing infrastructure position us well to meet demand. We’ve invested in manufacturing capabilities, ensuring we can scale effectively as needed. The ability to cryopreserve and ship CAR-NK cells globally is a testament to our preparedness to meet future demand, ensuring that our commercial capabilities match our scientific advancements. This dual focus on innovation and practicality ensures that we can deliver cutting-edge therapies without compromising on feasibility or accessibility. Our goal is to make these transformative treatments available to all who need them efficiently and sustainably.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
