Case Study: International Phase 1 Non-small Cell Lung Cancer (NSCLC) Trial

Non-small cell lung cancer (NSCLC) makes up 80-85% of all lung cancer, but RET fusion-positive NSCLC only occurs 1-2% of the population.^1,2 The prognosis is complicated for these individuals. Around 70% are already in stage IV when they are diagnosed, so they are more likely to develop metastasis and ultimately have a much poorer prognosis than other forms of cancer.³ In fact, 1 in 4 patients diagnosed with stage 4 NSCLC will not live past three months.⁴

In this article, we will look at the efforts of one sponsor and discuss how Precision for Medicine supported that research. We will also look at lessons learned and explore the important takeaways from the trial.

Study overview

This Phase I trial looked at tumors with RET gene alterations amongst patients with NSCLC or Medullary Thyroid Cancer (MTC). For this case study, we will focus on the work we performed for the trial as a whole and detail elements specific to the NSCLC segment as appropriate. 

Early phase oncology expertise in action

Our approach to the NSCLC trial was comprehensive. In overseeing the trial we implemented best practices informed by our expertise in oncology. Using our deep understanding of NSCLC, we kept a clear channel of communication with essential client contacts and vendors, ensuring shared objectives and a cooperative atmosphere. We achieved exceptional study retention thanks to our keen focus on the patient experience. The team’s knowledge of regional standards of care across and local relationships allowed them to streamline enrollment and site startup.  

In this NSCLC trial, our strategy was not just about managing the logistics of the trial, but about forging a path that was both innovative and adaptable to the changing landscape of oncology research. Here’s a deeper look into our strategic approach, broken down into its core elements:

Leveraging patient recruitment best practices

• Identifying Potential Patient Pools: Recognizing the limited availability of patients with the specific RET mutation, we focused on sites already conducting screenings as part of their standard care. This approach provided an initial pool of potential patients who were already engaged and informed about their condition. 
• Searching for Literature: Regular review of various RET related literature was key to determining if particular alterations documented for potential patients were indeed considered RET mutations and therefore the relevant patients likely to benefit from the treatment offered in the study. This helped reduce the potential dropout rate. 
• Reducing Screen Failure Rates: By tapping into this pre-screened population, we significantly minimized screen failures. This not only enhanced the efficiency of the trial but also ensured a faster recruitment process, crucial in the fast-paced field of oncology. 
• Impacting Patient Recruitment Dynamics: The strategy led to a nuanced understanding of the patient recruitment landscape, highlighting the importance of integrating pre-existing medical practices into the trial design to optimize patient enrollment. 
  
  

Adaptive site selection and geographical expansion

• Initial European Focus: The trial commenced with a strategic selection of sites in Belgium and France, chosen for their extensive experience and infrastructure in NSCLC trials, particularly with the RET mutation. 
• Inclusion of Diverse Regions: Recognizing the need for a more diverse patient population and facing challenges in patient availability, we expanded to include sites in the US, Spain, and crucially, the Asia-Pacific region. This decision was not merely about numbers; it was a strategic move to encompass a broader genetic and demographic representation in the trial. 
• Collaboration with Partner Companies: To facilitate this expansion, particularly in the Asia-Pacific, we turned to a partner. This partnership was instrumental in navigating regional complexities and ensuring compliance with local regulations, thus smoothing the process of site initiation and patient recruitment. 

Customized patient management and treatment delivery

• Formulation Transition from Capsules to Tablets: The switch to tablet formulation was a response to patient feedback and an effort to improve compliance. Higher dosage tablets reduced the number of pills patients had to consume daily, addressing both convenience and the psychological burden of treatment. 
• Patient-Centric Approach: This change exemplifies our commitment to a patient-centric approach in trial design. By acknowledging and addressing patient preferences and challenges, we enhanced participation satisfaction and adherence, ultimately leading to more reliable study data. 
• Continual Monitoring and Adjustment: The shift also demonstrated our flexibility in adapting trial protocols in response to emerging needs and patient feedback. This iterative approach ensured that the trial remained patient-friendly and scientifically robust. 

The success of this NSCLC trial was rooted not only in our technical capabilities but in our strategic foresight and adaptability. Our approach went beyond traditional trial management, embracing innovative patient recruitment strategies, adaptive site selection, and a deep commitment to patient-centric care. This trial stands as a testament to our ability to navigate the complexities of oncology trials, delivering results that are both scientifically valid and ethically sound.

Lessons learned

The NSCLC trial presented several critical lessons that are invaluable for future oncology trials, particularly those involving specific genetic mutations like the RET variation. Lessons learned were collated and discussed at 3 study timepoints: 

• Following completion of startup activities for dose escalation component of the study 
• Following completion of the dose escalation component of the study 
• Following database lock  

Strategic site & country selection based on standard of care 

• Importance of Screening Practices: Choosing sites and countries where screening for the RET mutation was part of the standard care was pivotal. This strategy significantly expedited the participant screening process, as many potential candidates were already identified and engaged. 

• Efficiency in Patient Recruitment: This approach minimized the time and resources typically required for patient identification and initial screening, highlighting the importance of aligning trial needs with existing healthcare practices. 

Adapting to global trial challenges 

• Expanding Beyond Initial Regions: Despite starting in select European countries, the necessity to increase patient numbers led to a strategic expansion into the US and Asia-Pacific regions. 
• Navigating Regional Variabilities: The expansion required adapting to different standards of care and patient management practices in each region, underscoring the importance of flexibility and local knowledge in global trials. 

Patient-centric formulation decisions 

• Transition to Patient-Friendly Formulations: The decision to switch from capsule to tablet formulations was driven by a commitment to patient convenience and compliance. 
• Balancing Dosing and Patient Comfort: Using an accelerated titration design to limit patient exposure to sub-optimal dose levels and managing the dosage requirements while minimizing the pill burden for patients showcased the trial’s focus on patient-centric approaches. 
  
  

Collaborative and Transparent Communication 

• Enhanced Stakeholder Engagement: Maintaining open lines of communication with all stakeholders ensured that the trial adapted swiftly to emerging challenges and opportunities, like exploring sites in Asia. 
• Building Trust Through Transparency: Regular updates and transparent discussions about trial progress and challenges fostered a collaborative environment, essential for the trial’s success. 

Navigating Vendor and Partner Relationships 

• Leveraging External Expertise: Partnering effectively with organizations and skilled trial personnel, particularly in the Asia-Pacific expansion and in our Spain sites, was crucial in identifying suitable sites and managing regional complexities. 
• Shared Goals and Objectives: Establishing clear and aligned objectives with all partners ensured cohesive efforts towards the trial’s success. 

Importance of Real-Time Data Management 

• Continuous Monitoring: The trial underscored the necessity for ongoing monitoring and data analysis, enabling timely interventions and adaptations. 
• Adapting to Evolving Data Requirements: The trial’s data management strategies had to evolve in real time, reflecting changes in patient profiles, formulation changes, and expanded site locations. 

The NSCLC trial, with its focus on patients with a specific RET mutation, provided profound insights into managing complex, multinational clinical trials. The lessons learned highlight the significance of strategic site selection based on standard care practices, the need for flexible and patient-centric approaches, and the value of collaborative and transparent communication across all levels of trial management. These insights are not only crucial for future NSCLC trials but also applicable to broader oncology research endeavors, providing a roadmap for efficient, effective, and ethically sound clinical trial management. 

Insights from this NSCLC clinical trial collaboration

This NSCLC trial provides practical insights into managing complex oncology studies, particularly those involving specific genetic mutations like the RET variation. 

Clinical Trial Achievements 

• Effective Enrollment and Management: The trial demonstrated effective patient enrollment and management, adapting to the varying medical standards and patient needs across different regions. This allowed first patient to be dosed just over 6 months after the final protocol was available. Note, the period covered both summer holidays and the winter celebratory period, which is significant due to the impact that time of year has on patient and site staff availability. As such, being able to dose patients so quickly is significant. 
• Strategic Patient Recruitment: Utilizing pre-existing screening practices for the RET mutation at selected sites drastically streamlined the patient recruitment process. 

Adapting to Global Clinical Trial Challenges 

• Geographical Expansion: The expansion from initial European sites to the US and Asia-Pacific regions highlighted the importance of understanding and responding to regional healthcare differences. 
• Managing Diverse Patient Populations: This geographical diversification provided insights into managing a trial across diverse patient populations with different healthcare access and standards. 

Patient-Centric Formulation Decisions 

• Formulation Adaptation for Patient Convenience: The switch from capsule to tablet formulations was a key decision that showcased the trial’s commitment to enhancing patient compliance and comfort. 
• Balancing Dosing and Patient Comfort: This change emphasized the need for ongoing monitoring and flexibility in trial protocols to meet emerging patient needs. 

Have an upcoming NSCLC study? Proceed with Precision

Our strategy in this NSCLC trial underscores the importance of flexibility, patient engagement, and collaborative efforts in the ever-evolving landscape of oncology research. It exemplifies our dedication to advancing NSCLC treatment and research, contributing significantly to the broader goal of enhancing patient care and outcomes in oncology. 

As your potential partner in NSCLC drug development, we at Precision for Medicine are committed to applying the insights gained from this trial to future oncology research. Our approach is grounded in practical strategies, patient-focused solutions, and collaborative efforts with global partners.

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References:

1. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-594. doi:10.4065/83.5.584
2. Andrini E, Mosca M, Galvani L, et al. Non-small-cell lung cancer: how to manage RET-positive disease. Drugs Context. 2022;11:2022-1-5. Published 2022 Jul 11. doi:10.7573/dic.2022-1-5
3. Shen Z, Qiu B, Li L, Yang B, Li G. Targeted therapy of RET fusion-positive non-small cell lung cancer. Front Oncol. 2022;12:1033484. Published 2022 Dec 13. doi:10.3389/fonc.2022.1033484
4. Guo H, Li H, Zhu L, Feng J, Huang X, Baak JPA. “How Long Have I Got?” in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question. Front Oncol. 2021;11:761042. Published 2021 Dec 21. doi:10.3389/fonc.2021.761042