The World Health Organization (WHO) estimates the number of new cancer cases per year will increase by an alarming 60% by 2040, highlighting the urgent need to develop more effective targeted oncology therapies. Since 1986, the use of immunotherapy (IO) agents in cancer treatment has seen significant expansion, and in 2022 alone, there was a record number of immuno-oncology targets (195) being investigated in cancer clinical trials. Broadly speaking, immunotherapy is defined as a type of targeted treatment that harnesses the immune system to help the body fight infections and other diseases, such as cancer. In recent years, the immunotherapy landscape has gradually shifted towards adopting a precision medicine approach. With this approach, technological advances in genetic testing, molecular diagnostics, and imaging have made it possible to use each patient’s DNA analysis, immune markers, and baseline comorbidities to help oncologists determine their optimal therapy.  

However, this groundbreaking evolution of personalized patient management also brings new challenges. Modern cancer clinical trials are growing in complexity and increasingly demanding greater specialized oncology expertise and robust operational capabilities. Contract research organizations (CROs) are playing a pivotal role in navigating these challenges, although selecting the right partner is a significant factor in trial success. This article will explore the five crucial aspects of modern oncology development programs, providing key insights to help sponsors optimize their immunotherapy and precision medicine trials in cancer research. Read on to learn more!

 

1. Strategic Cancer IO Trial Design Insights

Clinical trials have generally become more complex over the last few decades, but this especially rings true for cancer studies and even more so for cancer immunotherapy trials. Accordingly, the landscape of strategic trial design has also become increasingly sophisticated, particularly in immunotherapy research. Among the most popular are adaptive designs, which use accumulating data to modify various preplanned aspects of an ongoing trial to monitor the study’s progress while addressing any emerging statistical problems. For example, an immunotherapy trial can be adaptively designed for early termination after interim analysis of efficacy and futility if a treatment is found to provide no true benefit. This not only provides potentially significant cost and time savings, but also avoids needless patient participation burden.  

Adaptive trials are advantageous in that they address several shortcomings of randomized clinical trials (RCTs), including the need for a large sample size, long study duration, insufficient study power for important subgroup analysis, and prohibitive costs. However, sponsors should carefully weigh how implementing these designs might impact development timelines and anticipated resource allocation. For instance, an adaptive seamless phase 2/3 trial design allows for the possibility of early termination and can reduce the overall trial duration, cost, and sample size, but it typically demands more intensive upfront planning and real-time data analysis capabilities. Therefore, when selecting specific adaptive methodologies, such as the Modified Toxicity Probability Interval (mTPI-2) study design or Bayesian Optimal Interval (BOIN) designs, sponsors must consider several factors, including the therapeutic mechanism, expected toxicity profiles, and trial objectives.  

For these reasons, it is crucial to evaluate a potential CRO partner’s expertise in strategic trial designs based on an assessment of concrete metrics. Sponsors should review the CRO’s track record with similar adaptive designs, determine the extent of their statistical programming capabilities, and any prior experiences with implementing preplanned protocol changes after interim analysis. Various key performance indicators should also be considered, such as successful protocol amendment rates, time from design finalization to the First Patient In (FPI) milestone, as well as the accuracy of interim analyses in previous adaptive trials. 

Interested in learning more about adaptive trial designs? Click here to read about how BOIN designs are accelerating early phase brain tumor clinical trials, or visit this page to explore the mTPI-2 study design.  

 

2. Specific Operational Requirements for IO Therapies

Modern cancer immunotherapy trials present rigorous operational challenges that require a wide variety of niche expertise and robust infrastructure. The result is a particularly intricate vendor landscape that often involves multiple specialized laboratories for biomarker testing, complex imaging facilities, and well-coordinated supply chain management for temperature-sensitive biological materials. These services span several different vendor types, from high-capacity central labs through diverse biorepositories to rapid courier services.  

Additionally, because cancer immunotherapeutic drugs exert their anticancer effects by modulating the immune system, they are associated with unique adverse event (AE) profiles. Therefore, it is critical for IO trials to be especially vigilant about their safety monitoring requirements. Sponsors and safety vendors must ensure they have taken steps to implement reliable active AE reporting systems that offer 24/7 medical monitoring capabilities, as well as establish rapid response protocols for immune-related AEs (irAEs). When evaluating a potential partner CRO’s capabilities for the stringent operational requirements of IO clinical trials, sponsors should consider the following key performance metrics:  

• The CRO’s experience in managing similar trial complexities, as measured by the number of successfully completed IO trials.  
• Their demonstrated expertise in irAE management, which should be reflected in the CRO’s safety reporting timelines and quality metrics. 
• Any established relationships with various vendor types, as evidenced by successful past collaborations and standardized processes.  
• A reliable track record of maintaining dedicated cancer IO trial teams with specialized training and documented experience in managing the unique challenges of these studies. 

These considerations are crucial for timely communication of safety information throughout the entire study lifecycle, ensuring subject safety in clinical trials. Therefore, sponsors must carefully select a CRO partner with the right safety monitoring capabilities for cancer IO development.  

For more information, visit this draft guidance from the US FDA for characterizing, collecting, and reporting immune-mediated adverse reactions in cancer immunotherapeutic clinical trials. 

 

3. Biomarker Strategy Considerations in Precision Oncology IO Trials

Despite the rapid evolution of oncology therapeutic development seen in recent decades, many investigational drugs continue to fail during clinical trial testing. Biomarker development and testing may offer researchers an exciting opportunity to improve the chances of a compound moving forward in the development pipeline. Notably, this 2015 study of 1,079 oncology drugs found that success rates for cancer drugs developed with biomarkers were four times as high as those of compounds developed without biomarkers (24% vs. 6%, respectively). Biomarkers play a particularly important role in cancer immunotherapeutic trials because the precision medicine approach heavily relies on them to help identify patients who may or may not respond to certain targeted drugs.  

However, in terms of implementation challenges, there are often obstacles posed by the complexity of biomarker validation and standardization across multiple trial sites. Multi-omics (i.e., encompassing genomic, proteomic, transcriptomic, and/or metabolomic data) studies also produce massive volumes of data, requiring substantial computational resources for storage, processing, and analysis. Other challenges associated with biomarker implementation include limited availability and accessibility of these datasets, the need for sophisticated statistical expertise and algorithms, and difficulties with interpreting complex biological interactions. 

Mitigating these challenges will require vendors with the appropriate infrastructure, including specialized laboratory networks, real-time data integration systems, and advanced analytics platforms. Furthermore, because biomarker datasets are generated on a global scale, accessing them will depend on whether there are effective data-sharing policies and platforms in place to facilitate greater collaboration. Sponsors must also consider whether their potential CRO partner has demonstrated capabilities in handling multi-omic data sets, managing complex specimen logistics, and implementing robust chain of custody procedures.  

Other useful vendor features that could boost your cancer IO trial’s biomarker strategy include leveraging different machine learning (ML) algorithms to optimize biomarker classification, performing regular quality checks to ensure data reproducibility and reusability, rapid validation of identified biomarkers, and scalable cloud-based infrastructure for efficient, cost-effective sample processing. Learn more here about common challenges in practice when conducting biomarker-guided clinical trials.  

 

4. Key Selection Criteria for Choosing an Appropriate CRO Partner

As we’ve discussed throughout this article, selecting the right CRO partner for immunotherapy trials requires a systematic evaluation approach based on quantifiable metrics and demonstrated expertise. Specifically, sponsors should utilize the following indicators, among others, to help assess whether a potential CRO possesses appropriate expertise in IO trials: 

• The number of completed IO trials within the past five years 
• Success rates in similar indications 
• The complexity of trials managed in the past 
• A clinical trial portfolio that lists a balanced mix of early and late-phase IO trials, ideally with a sizeable portion dedicated to complex biomarker-driven studies 
• The extent of personnel expertise, as measured by years of IO-specific experience and the number of specialized certifications 
• The extent of international clinical and regulatory experience across various global regions 

A technological capabilities assessment should also be conducted against the IO program’s unique needs. For example, the CRO should be able to provide readily established eClinical systems, biomarker testing facilities, and cross-functional data management platforms with real-time data integration features. Additionally, sponsors are encouraged to complete a thorough review of their quality management system to ensure robust quality control processes. The right CRO will show promising key performance indicators, such as a low rate of critical protocol deviations and relatively fast site initiation timelines that surpass industry averages. Ideally, they will also have a strong existing network of relationships with reliable vendors, well-documented standard operating procedures (SOPs) for navigating IO-specific challenges, and even a success track record of implementing adaptive trial designs efficiently.  

For more detailed guidance on how you can select the right CRO for your next oncology clinical trial, click here. 

 

5. Best Practices for Successful Cancer IO Clinical Trials

Finally, sponsors may consider developing a comprehensive framework for CRO evaluation and robust performance monitoring for successful execution of immunotherapy trials. Specifically, when evaluating potential CRO partners, a structured approach is recommended, covering three critical aspects of the organization’s potential capabilities discussed earlier: technical capabilities, operational experience, and quality metrics. By collaborating with a cancer CRO with long-standing IO-related expertise rather than a general oncology CRO, immunotherapy trials could also possibly benefit from more targeted patient recruitment strategies and reduced rates of protocol amendments or protocol deviations.  

Key factors that impact the chances of success in IO trial execution include establishing tailored training programs for site staff to reduce protocol deviation rates, implementing IO-specific risk management strategies, and maintaining flexible resourcing models to accommodate changes specifically expected from adaptive trial designs. Sponsors can also compare the CRO’s various performance benchmarks against industry averages. For example, leading CROs tend to have low rates of missing data, and often, their site initiation timelines are well below the industry average (~305 days for interventional trials). Further, they may be able to achieve database lock within a few weeks of the last patient visit, as well as demonstrate consistency in adequate patient retention rates, query resolution times, and time to FPI (ideally within 30 to 60 days of site activation). Overall, regular performance reviews using these types of standardized metrics can help track continuous improvement and identify potential issues earlier in the trial lifecycle.  

 

Conclusion 

As the therapeutic landscape of cancer immunotherapies and precision oncology approaches continue to evolve rapidly, there are several key considerations for sponsors conducting IO clinical trials. Ultimately, achieving success with such complex studies relies on finding CROs with demonstrated long-standing IO expertise, robust operational capabilities, and sophisticated biomarker strategies. Establishing a strong sponsor-CRO relationship remains a key factor in advancing cancer immunotherapy clinical trials and these approaches can be used to optimize trial outcomes, while ensuring patient safety.  

 

TFS HealthScience: Your Global CRO Partner in Oncology & Hematology  

TFS HealthScience Oncology & Hematology CRO is dedicated to providing comprehensive services to support your oncology clinical trials. With a proven track record of over 300 cancer-related clinical trials across all phases globally, we’re committed to delivering solutions that match your needs. Our global operations teams are fully experienced with navigating the complex landscape of cancer clinical research, offering rigorous operational oversight and adherence to global standards. Visit our oncology CRO website to learn more or connect with a TFS representative here! 

To learn more about the expertise that TFS Oncology & Hematology CRO can offer for your next cancer trial, visit our page here.  

Interested in more Oncology and Hematology CRO content from TFS? Visit our Intellect Hub here to access white papers, articles, case studies, and more!