Cancer rates continue to rise globally, creating an urgent need for more effective and innovative treatments. Traditional approaches like chemotherapy and radiation (while still important) are often not enough to address the growing burden and complexity of cancer.
Immuno-oncology (IO) therapies, which harness the body’s own immune system to combat cancer, have emerged at the forefront of modern cancer treatment. Building on decades of foundational research, IO approaches such as immune checkpoint inhibitors and cell-based therapies, have rapidly become standard of care for multiple malignancies. These advances are not only offering new hope to patients but are also fundamentally reshaping the oncology landscape, driving a paradigm shift toward more personalized and durable treatment strategies.
The rise of immuno-oncology
The concept of using the immune system to fight cancer existed for over a century, but meaningful progress accelerated in recent decades with the discovery that cancer cells evade immune detection by activating inhibitory pathways—effectively applying “brakes” to the immune response. A breakthrough occurred in 2011 when the first immune checkpoint inhibitor, ipilimumab, was approved for advanced melanoma. This milestone demonstrated that releasing these brakes could unleash the immune system’s ability to recognize and attack cancer, marking the beginning of a new era in oncology.
Today, IO encompasses a diverse range of modalities, including:
- Checkpoint inhibitors (CPIs)
- Cellular therapies (CAR-T, TILs)
- Multispecific T-cell engagers (TCEs)
- Tumor microenvironment (TME) remodelers
- Oncolytic viruses
- Vaccines and gene therapies
Despite significant advances in immunotherapy, many patients exhibit limited or no response, and certain tumor types remain highly resistant to immune-mediated attack. This variability is often driven by factors such as tumor microenvironment complexity, immune evasion strategies, and patient-specific biology. To address these barriers, researchers are actively investigating novel approaches including next-generation immune modulators, personalized vaccines, and rational combination regimens—all to enhance efficacy and broaden the benefit across diverse cancer populations.
Key challenges in IO trials
While IO therapies have transformed cancer care, developing and executing these trials presents unique complexities. Sponsors and sites must navigate novel safety risks, manage intricate biomarker-driven designs, and overcome operational hurdles such as specialized logistics and regulatory requirements. These challenges underscore the need for innovative trial strategies and close collaboration to ensure that promising therapies reach patients efficiently and safely.
Complex modalities and logistics
IO trials often involve live cells or viruses, each with unique handling, storage, and administration requirements. Cell therapies, for example, require rigorous chain-of-custody tracking, specialized manufacturing and coordination across multiple vendors and clinical teams.
Safety and toxicity management
While IO therapies can deliver durable responses, they also introduce new safety concerns. Acute toxicities such as cytokine release syndrome (CRS), neurotoxicity (ICANS), and tumor lysis syndrome (TLS) are more common with cell therapies and TCEs. Immune-related adverse events (irAEs) like colitis, pneumonitis, or hepatitis can occur with CPIs and TME remodelers. Regardless, specialized monitoring and rapid intervention are required.
Novel endpoints and study designs
Traditional response criteria may not capture the unique patterns of IO activity. Novel endpoints such as iRECIST, and adaptive designs like BOIN and mTPI, are increasingly used to better assess efficacy and manage patient cohorts. Longer follow-up periods are needed to capture durable responses and/or delayed onset of post-treatment toxicities.
Patient selection and recruitment
IO trials often require biomarker-driven eligibility, complex screening, and sometimes access to specialized centers. Early strategic planning, a robust global site network, and innovative recruitment strategies are critical to success.
Best practices and lessons learned
Ensuring success in IO trials requires a focused set of best practices. By leveraging highly experienced teams, anticipating operational complexities, and prioritizing both patient safety and scientific innovation, we help sponsors navigate the unique demands of immuno-oncology studies. This approach enables efficient trial execution and accelerates the delivery of transformative therapies to patients.
Leverage experienced sites and teams
Experienced sites are critical for managing the unique toxicities and logistics of IO trials. Cell therapies and TCEs often necessitate academic centers with ICU support and overnight monitoring.
Plan for operational complexity
From chain-of-custody documentation to managing multiple informed consents, IO trials demand meticulous planning and coordination. Early engagement with vendors, clear communication, and contingency planning are essential.
Prioritize safety and data quality
Given the high rate of adverse events and the need for long-term follow-up, robust safety monitoring and real-time data review are non-negotiable.
Embrace innovation
The IO landscape is evolving rapidly, with new modalities, endpoints, and regulatory expectations. Flexibility, a data-centric approach, and a willingness to adapt protocols as science advances are key to staying ahead.
We quickly recognized that there was no margin for error or further delays due to the patient’s rapidly declining status. When this emergency arose, our team jumped into action, partnering with manufacturing and other key study members to determine the root cause and implement a rapid solution. Thanks to that responsive, decisive approach, the patient’s cells arrived on time and treatment moved forward safely, protecting both the patient’s outcome and the integrity of the study.
Susan Albert
The path forward
IO is transforming cancer treatment, offering new hope to patients with previously untreatable diseases. Yet, the path from bench to bedside is complex, requiring deep expertise, operational excellence, and a relentless focus on patient safety. At Catalyst Oncology, IO represents more than 40% of our active portfolio, and our commitment to advancing these therapies is stronger than ever.
Ready to accelerate your IO program?
Discover how Catalyst Oncology can support your next Immuno-Oncology trial by contacting us today.
