The NCT04886804 study is divided into two parts to investigate BI 1810631’s safety and efficacy in different patient groups. The first part is open to adult patients with various advanced solid tumors exhibiting changes in the HER2 gene. These participants had experienced treatment failures with prior therapies. The primary objective of this stage is to determine the highest tolerable dose of BI 1810631 that patients can handle.
Once the optimal dose is established, the second part of the study focuses on patients with non-small cell lung cancer (NSCLC) specifically harbouring exon20 insertions. In this phase, the researchers aim to evaluate whether BI 1810631 can induce tumor shrinkage, potentially providing a much-needed treatment option for this specific subset of patients.
Administration and Monitoring
Participants in the NCT04886804 trial received BI 1810631 orally in the form of tablets. The medication can be taken once or twice daily, depending on the treatment regimen assigned to each patient. Since BI 1810631 has been administered to patients for the first time in this study, careful monitoring of participants’ health and tumor response is essential.
Patients will remain in the study for as long as they continue to benefit from and tolerate the treatment. Regular health checks and tumor assessments are being conducted by study doctors to closely monitor patients’ progress. Additionally, any adverse effects attributed to BI 1810631 are diligently recorded and analyzed.
Promising Results
The interim analysis of the NCT04886804 study has shown promising outcomes. Dr. Frans Opdam, the study principal investigator, shares that in patients with non-small cell lung cancer with specific exon20 insertions, the response rate has been 46%, with a median duration of response close to 7 months. Furthermore, patients with other tumor types exhibiting HER2 amplification/overexpression or mutations have displayed a commendable response rate of 37%.
Moreover, BI 1810631 has been well-tolerated by the participants, with grade 1 diarrhea being the most common side effect reported. The ability to minimize debilitating side effects is crucial in enhancing patients’ quality of life and compliance with treatment.
Future Implications
These early results from the NCT04886804 study have generated significant enthusiasm among oncologists and the medical community. The potential for BI 1810631 to become a highly effective and well-tolerated treatment option for patients with advanced HER2-altered solid tumors, including non-small cell lung cancer, is bringing us great hope.
Nonetheless, while these findings are highly encouraging, it is important to acknowledge that the study is still in its early phases, and further research and larger patient cohorts are required to validate the efficacy and safety of BI 1810631.
M22TGA: A NOVEL IN-HOUSE PHASE I CLINICAL TRIAL FOR PATIENTS WITH ADVANCED CRC AND PERITONEAL METASTASES
Medical innovations often emerge from constant dedication and original approaches. The M22TGA study, currently being conducted at the Antoni van Leeuwenhoek Hospital and the Netherlands Cancer Institute (NKI), is a great example of this spirit.
Leading this study is Ashwini Kanhailal, a distinguished young medical doctor with specialised interests in oncology and research. After an enriching experience at the OLVG hospital, Ashwini is contributing significant expertise to the M22TGA research.
“As I was interested in oncology and research I got the opportunity last year to start my PhD program at the NKI. I’m mainly focused on combination therapy in phase I clinical trials.”
Ashwini’s journey started with merging academic curiosity and practical application, which enabled her to steer the M22TGA trial with precision and innovation.
Unique In-House Development
What sets the M22TGA study apart from other trials is its origin. Unlike many clinical trials that start from large pharmaceutical companies, the M22TGA is entirely an in-house brainchild of NKI. From pre-clinical findings to study design to drug production, thanks also to the collaboration with Amsterdam UMC, NKI shows that even smaller Phase I units can be at the forefront of oncological research.
Study Rationale
Study Design
Encompassing both Phase I and II, the M22TGA study is meticulously designed. While the first phase delves into the combination therapy’s safety and tolerability, the latter phase rigorously evaluates its anti-tumor prowess. In both phases, the recommended dosage of galunisertib is combined with the standard dosage of capecitabine. Operating on a ‘proof of principle’ basis, this non-randomized, open-label study is currently active at the Antoni van Leeuwenhoek Hospital and will soon be available at the Amsterdam UMC.
Study population and patient referral
The total number of patients that can be recruited for phase I are 6, while the other 25 are allowed on phase II. As Ashwini explained to us, there are currently just 3 spots taken out of 31. It is now indeed a great opportunity for you to refer your patients that qualify for participation in this study.
To do so, contact the phase I department of the Antoni van Leeuwenhoek Hospital, by emailing us at fase1@nki.nl. Please, refer to the phase I email address for any questions regarding the study and/or study procedures.
‘I have to make sure that all the operational processes are done in the right way, by enough people in the right place and at the right moment’
Lieke emphasizes the need for efficient and effective operational processes, ensuring that each step is executed accurately and at the right time. Collaborating closely with the quality officer, she upholds the institute’s commitment to excellence and patient well-being.
How to successfully set up a clinical trial?
The initiation of any trial at the CRU starts with a rigorous feasibility assessment, which is the first contact between the pharmaceutical company and the institute, followed by an official site selection visit where it is established what is needed to have the trial up and running, including the contractual agreement, the financial and ethical consents.
Securing ethical approval is one of the most time-intensive steps during the start-up phase. The detailed review and multiple iterations with the ethical committee often extend over several months. Ethical approval stands as a non-negotiable criterion; without it, the trial cannot commence. In parallel, the financial aspect cannot be overlooked and needs to be finalized before progressing any further
Lieke emphasizes the importance of capacity management. Already in these early stages in the start-up phase, 90% of equipment and devices need to be suitable for the trial, while the institute’s human resources shall be adeptly trained and allocated.
Despite the use of capacity management tools and meticulous planning, some aspects are beyond NKI’s control, including some ethical procedures. These delays often stretch the start-up phase over extended periods, which is why adaptability, communication, and the collective efforts of various parties are fundamental in navigating these challenges in a timely manner.
Transitioning from Initial Setup to Operational Efficiency: Blood Sample Management in Clinical Trials
As the study progresses to the ‘active’ stage – often denoted as cycle 1, day 1 – blood samples are collected just prior to administering the IMP and continue to be taken at various time points, sometimes for as many as three consecutive days.
In phase 1 and 2 clinical trials, the collection of blood samples for analysis is a core component. These samples help assess if and how tolerable, safe and effective the IMP is. The blood samples need to be collected on various time points throughout the entire treatment according to detailed protocols. Managing blood samples, (processing, worldwide shipping and stakeholder alignment), is a intricate process that necessitates the concerted efforts of the hospital, the central laboratory, providing pharmacokinetic material and protocols, and the pharmaceutical entities.
Alongside with securing a smooth cross-collaboration, Lieke is responsible for ensuring that every individual at CRU – from lab technicians to research scientists – is not only trained but is also consistently updated on lab manual procedures and protocols. These rules are almost continually subject to modification due to evolving methodologies, regulatory updates, or stakeholder requests. “It’s not just about getting everyone up to speed but keeping them there, especially as best practices evolve,” Lieke adds
‘It’s so trial-specific what we have to do and how we do it. Every trial is a new chance to improve or to maintain a level of quality’
Each clinical trial presents its own unique set of challenges, leading to the need of distinct protocols and instructions. This complexity demands robust coordination, extensive training of all staff and commitment to preserve the highest standards of quality.
Lieke verifies that all internal departments are aligned (pathology, triallab, radiology, pharmacy amongst others) and that every team member is fully informed of their roles and details inherent to each trial. Given the unique nature of every trial but especially with patient safety as top priority, it is essential to keep the research team updated and aligned by regular training sessions and meetings. External partnerships are also managed to maintain a synergistic collaboration.
‘If there is any issue or safety concern, we communicate immediately with the pharmaceutical company or its clinical research associate (CRA)’
From the very beginning of the trial, there is a consistent open line of communication with the pharmaceutical entity’s CRA, who is responsible for answering any questions about safety or administration, and contacting the medical team to support any adverse circumstance. In the end, patient safety and adherence to the trial’s protocol are everyone’s top priorities!
Setting the standard: what we can learn from successful trials
Lieke recounts an exemplary initiation of a trial: “Two years ago we started a trial that was very complex to set up, due to the several treatment arms and the high number of amendments. Nonetheless, it showed actual results already during its primary end-point. Thanks to the data collected and the rigorous assessments we could reckon that the administered IMP was eligible for compassionate use outside the trial settings. This study is still active for further investigations/research, and the IMP is currently accessible.
The success of this study was determined not only by the efficiency in data collection and analysis, but also by a strong execution and close collaboration among all involved parties”.
As there are currently more than 60 active studies open for inclusion at the CRU, NKI offers a trial for each patient type. Given the complexity of creating customized protocols, the time spent and the number of people involved in a trial, to help us maintain success and efficiency we ask doctors that want to refer a patient to be aware of the inclusion criteria and the deadlines well in advance.
For a comprehensive understanding of the clinical backgrounds, and the intricacies of patient referral and selection, we invite our readers to stay informed via updates on our website.
