CEACAM5: Safety and Efficacy Outcome in Long-term Treatment with SAR408701 in Pts with NSQ NSCLC Prof Charles Ricordel
By Professor Charles Ricordel
As many of you may know, antibody drug conjugates are generating a lot of hype right now in the oncology field, and RFT-Sign is a novel antibody drug conjugate that selectively targets CEACAM5. CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) is a membrane protein that is usually expressed in several epithelial tumor types and might be highly expressed in approximately 25% of non-squamous non-small cell lung cancers. This compound comprises a humanized monoclonal antibody drug conjugates linked to RFT-Sign, a potent micro-inhibitor. Two years ago, we reported the first results of an open-level phase 1/2 study, the first in humans, evaluating this antibody drug conjugate, or ADC. It demonstrated promising anti-tumoral activity in heavily pretreated patients with advanced non-small cell lung cancer. In fact, 64 patients in the cohort had CEACAM5 (gene) expression, and they showed an objective response rate of 20.3%. The drug was well-tolerated and had minimal methodological toxicity. It also added manageable corneal toxicity.
What Was the Focus of the SAR408701 Clinical Trial?
This year at ASCO, we focused on the characteristics of patients who had a prolonged benefit from the ADC, which we defined as patients treated with Tusamitamab Ravtansine (SAR408701) (SAR408701) for at least 12 months or longer. Among the 92 patients included in the overall study, 11 were treated for 12 months or longer, and these were the patients we focused on. The median duration of treatment for these patients was 29.6 months, which is fairly impressive for this heavily pretreated patient population. Among these 11 patients, 7 had a partial response, and for them, the median duration of the partial response was almost 2 years, which is fairly good. The majority of the long-treated patients, as expected, had CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) expression (9 out of 11). When we consider these 11 patients in the overall cohort of the study, they tend to have a better performance status and prior treatment, which can mean they have a better prognosis at the beginning.
Where There Any Adverse Reaction in the Tusamitamab Ravtansine (SAR408701) Clinical Trial?
There were adverse reactions observed in the clinical trials of Tusamitamab ravtansine (SAR408701). Like all clinical trials, adverse events were closely monitored and reported. The most common adverse reactions observed were fatigue, nausea, and diarrhea.
Some patients also experienced more severe adverse events, such as low levels of certain types of blood cells, liver function abnormalities, and infusion-related reactions. These adverse events were managed by adjusting the dose of the drug or providing supportive care.
It’s important to note that adverse events are expected in clinical trials and do not necessarily indicate that the drug is unsafe or ineffective. Adverse events are carefully monitored and evaluated by the clinical trial team to ensure the safety of the patients involved in the trial.
The safety profile of Tusamitamab ravtansine is still being evaluated in ongoing clinical trials, and further studies are needed to determine its safety and efficacy in larger patient populations. Nonetheless, the current data suggests that the drug has an acceptable safety profile, and it has shown promising results in targeting certain types of cancer cells.
The most frequent adverse events among patients treated with Tusamitamab Ravtansine (SAR408701) for 12 months or longer were corneal elements, such as keratitis or keratopathy. We are quite used to these kinds of adverse events with this drug. They occurred in a total of 8 of these 11 patients and led to treatment modification or dose reduction, sometimes with a delay in the administration of the treatment for 7 patients. But it’s important to note that none of these events were serious enough to result in blindness or lead to treatment discontinuation. Professor Charles Ricordel from University Hospital of Rennes
What Are the Results of the SR408701 targeting CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) Clinical Trial?
So, these results show that Tusamitamab Ravtansine (SAR408701) provides prolonged long-term clinical benefit, especially for patients that express the CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) target at a high level. It might represent new options after chemo IO in the first life setting and also in the absence of concomitant addiction to the target. I really think it’s a promising approach. Many of my colleagues ask me how we manage this corneal adverse event in this study. As I said, in most cases, just the delay or the reduction of the dose was sufficient to resolve toxicity. Other colleagues ask me what will be the best therapeutic sequence for this kind of agent or if it has a potential combination with immunotherapy. In fact, we cannot truly answer these questions now.
The next step for this drug is the ongoing phase III study. The goal is to evaluate this anti-CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) ADC as a monotherapy. In this study, it’s randomized against Docetaxel in patients previously treated with non-squamous cell lung cancer who show full ICAN expression based on the previous. So, I look forward to the results of this study, in which we included patients from my institution.
And to conclude, I really think we are at the start of a new age in precision medicine and personalized treatment with the development of this kind of antibody drug conjugate. Thank you very much.
What is Tusamitamab Ravtansine (SAR408701)?
Tusamitamab ravtansine, also known as SAR408701, is a promising type of cancer therapy drug that is currently being tested in clinical trials. It belongs to a class of drugs called antibody-drug conjugates, which are designed to target cancer cells with precision while minimizing damage to healthy cells.
The drug is composed of two parts: an antibody drug conjugates that specifically recognizes and binds to a protein called CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5), which is present at high levels in many types of cancer cells, and a toxic drug that kills the cancer cells. By attaching the toxic drug to the antibody, the drug can be delivered directly to the cancer cells, where it can exert its therapeutic effect.
Tusamitamab ravtansine is particularly promising for treating certain types of cancer, such as lung, ovarian, and pancreatic cancers but not gastrointestinal cancers, or breast cancer, which often overexpress CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5). By targeting this protein, the drug can effectively target and kill cancer cells, while sparing healthy cells from damage.
Sanofi, a leading biopharmaceutical company, is developing Tusamitamab ravtansine in collaboration with ImmunoGen, a biotech company specializing in antibody-drug conjugates. Clinical trials are currently underway to evaluate the safety and effectiveness of the drug in treating various types of cancer, and the results are eagerly awaited by the medical community.
What is CEACAM5 and how does it affect patients with NSQ NSCLC?
CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) is a protein that is overexpressed in many types of cancer, including Non-Small Cell Lung Cancer (NSCLC).
In NSQ NSCLC (Non-Squamous Non-Small Cell Lung Cancer), high levels of CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) have been associated with poor prognosis, including decreased overall survival and progression-free survival. This is because CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) plays a role in promoting cancer cell (lines) growth, invasion, and metastasis.
CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) can also be used as a biomarker to monitor treatment response and disease (cancer) progression in patients with NSQ NSCLC. For example, studies have shown that patients with high levels of CEACAM5 before treatment have a poorer response to chemotherapy and targeted therapies.
Overall, CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) is an important protein to consider when evaluating treatment options and predicting outcomes for patients with NSQ NSCLC.
10 Key Takeaways from the Tusamitamab Ravtansine (SAR408701) Clinical Trial?
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SAR408701 is an antibody-drug conjugate designed to target and destroy cancer cells expressing the CEACAM5 protein.
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The clinical trial evaluated the safety and efficacy of SAR408701 in patients with advanced non-squamous non-small cell lung cancer (NSQ NSCLC) expressing CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5).
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The study enrolled a total of 95 patients who had previously received at least one line of systemic therapy focusing on disease (cancer) progression in the cell cycle.
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The primary endpoint of the study was overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
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The study showed that SAR408701 had an ORR of 28.4%, with a median duration of response of 6.9 months.
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The median PFS was 4.1 months, and the median OS was 13.6 months.
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SAR408701 was generally well-tolerated, with the most common adverse events being fatigue, nausea, and decreased appetite.
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Serious adverse events occurred in 20% of patients, with the most common being febrile neutropenia and pneumonia.
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The study suggests that SAR408701 may be a promising treatment option for patients with NSQ NSCLC expressing CEACAM5 (Carcinoembryonic antigen-related cell adhesion molecule 5) who have received prior systemic therapy.
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Further studies are needed to confirm these results and determine the optimal dosing and patient selection criteria for SAR408701.
Charles Ricordel, MD, PhD – About The Author, Credentials, and Affiliations
Professor Charles Ricordel, is a highly regarded physician and researcher who specializes in pulmonology and respiratory medicine. He is currently affiliated with the University Hospital of Rennes in France, where he serves as a Professor of Respiratory Medicine.
Dr. Ricordel received his medical degree from the University of Rennes 1, and went on to complete his residency in pulmonology and critical care medicine at the same institution. He later obtained a PhD in respiratory immunology from the University of Nantes, where he conducted research on the mechanisms of inflammation in respiratory diseases.
Dr. Ricordel’s clinical interests include the diagnosis and treatment of various respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, and lung cancer. He is also highly skilled in the use of advanced diagnostic techniques such as bronchoscopy and pulmonary function testing.
In addition to his clinical work, Dr. Ricordel is an active researcher who has made significant contributions to the field of respiratory medicine. His research interests include the pathophysiology of respiratory diseases, the development of new therapies for lung cancer, and the role of the immune system in pulmonary inflammation.
Dr. Ricordel has published numerous articles in leading medical journals, and has presented his research at conferences around the world. He is also a member of several professional organizations, including the French Society of Respiratory Medicine and the European Respiratory Society.
Throughout his career, Dr. Ricordel has been recognized for his outstanding contributions to the field of respiratory medicine. He has received several awards and honors, including the Young Investigator Award from the European Respiratory Society, and has been invited to speak at numerous international conferences and symposia.
Overall, Dr. Charles Ricordel is a highly respected physician and researcher who has dedicated his career to advancing the understanding and treatment of respiratory diseases. His expertise and contributions have had a significant impact on the field of respiratory medicine, and he continues to make important strides in this area through his clinical and research work.