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Marwa Noaman – Director of Clinical Operations, D2V Clinical 

Hello, everyone! My name is Marwa Noaman and I am the Clinical Operations Director here at D2V Clinical. 

As we all know, accurate data is crucial for driving innovation and advancing novel therapies. Today, we will explore how instream data cleaning is revolutionizing the way we ensure data quality, and our process for using this technique here at D2V Clinical. 

The process of instream data cleaning is to clean data and identify issues in as close to real time as possible over the entire course of the study. Performing statistical review is a critical step in the process. Data should quickly be analysis ready for multiple data cuts, such as data monitoring committee (DMC) meetings, dose escalation decisions, regulatory objectives, and database lock at the study completion. 

The instream data cleaning strategy involves collaboration with the entire study team to ensure statistical reviews are focused on cross CRF (Case Report Form) page, and cross data source reviews. For example, medical history and pre-treatment AEs (Adverse Events) will be reviewed together to check if the comorbidity of the enrolled population meets protocol assumptions. Correlation between safety endpoints and comorbidity will be examined if a potential trend is observed.  

Now that we have explored the power of instream data cleaning and its implementation at D2V Clinical, I will hand the floor over to our Chief Medical Officer, Dr. Vijay Reddy. 

Vijay Reddy, M.D., Ph.D. – Chief Medical Officer, D2V Clinical 

Hi, I am Dr. Vijay Reddy, the Chief Medical Officer at D2V Clinical. I oversee the implementation of instream data cleaning to ensure that our early-phase clinical research trials meet accurate and reliable data. Here is how we utilize these results from a medical perspective. 

Instream data cleaning supports the following 5 areas and more: 

• Data-driven Decision Making 
• Real-time Monitoring 
• Enhancing Protocol Adherence 
• Improved Patient Care 
• Accelerating Research Insights 

The best examples that were already alluded to are for efficacy and safety from a clinical perspective. The overall response rate (ORR) is a critical key endpoint for clinical trials, particularly as measured for efficacy. Instream data cleaning supports this through accurate documenting and verification of the RECIST criteria for efficacy measurement.

In addition, safety with CTCAE criteria documentation is critical, and instream cleaning supports that while enhancing data quality of both clinical and lab parameters.

Instream data cleaning is revolutionizing early-phase clinical trials, empowering researchers to make data-driven decisions. To learn more about D2V Clinical’s innovative instream data cleaning solutions, contact us today at d2vclinical.com. 

Hi, I’m Dr. Vijay Reddy, the Chief Medical Officer of D2V Clinical. 

Today, let’s explore Project Optimus, initiated by the FDA (Food and Drug Administration), which is a transformative effort to expedite the development and approval of innovative oncology treatments. 

As cited by the Oncology Center of Excellence (OCE) at the FDA, scientific progress has led to the development of entirely new classes of targeted drugs with different properties than traditional cytotoxic chemotherapies. Due to these advanced therapies, many patients, including those with advanced cancer, are living longer. Patients also want to live well, and their expectations are to receive more tolerable and efficacious drugs. 

However, not every targeted drug that enters a phase I clinical trial receives marketing approval, and poor dose optimization may be one reason for this. Historically, dose selection for oncology drugs was often based on a “more is better” paradigm. This is because, traditionally, drugs have been tested on an MTD (maximum tolerated dose) approach.  

The mission of Project Optimus is to ensure that doses of oncology drugs are optimized to maximize efficacy as well as safety and tolerability. One could say this is a “less is more” approach, emphasizing the need for better dose selection for oncology drugs. Therefore, a focus on dose optimization is an essential component of oncology drug development and is necessary to realize the promise of targeted therapies.  

The key principles to identify an optimized dose now include a paradigm shift from an MTD approach to the selection of several doses based on pharmacokinetic (PK) and pharmacodynamic (PD) data, as well as preliminary information regarding activity, safety, and tolerability.  

The doses can be evaluated more thoroughly, preferably early in development with randomized evaluations of multiple doses, to obtain a more comprehensive assessment of dose-response and exposure-response relationships for efficacy, safety, and tolerability. These evaluations will, in turn, inform the dose or doses for a registration trial and eventual drug approval. As mentioned by the FDA, focusing on dose optimization starting early in clinical development rather than in the post-marketing setting will allow more efficient identification of an optimal dose. 

In conclusion, the success of Project Optimus hinges on fostering collaboration and knowledge sharing among researchers, sponsors, and regulatory bodies. As clinical research professionals, embracing Project Optimus offers immense potential for accelerated drug development, patient-centered trials, and transformative breakthroughs in cancer therapies. 

If you would like to learn more about Project Optimus and how it may impact your drug development program, contact us at d2vclinical.com to connect with our experts. 

Hi, I’m Jill Loftiss, and I work for D2V Clinical, a CRO handling early-phase oncology and hematology programs. Today let’s talk about the positioning of our pharmacokinetic (PK) package within our New Drug Application (NDA).

There is a lot of difference between oncology and non-oncology programs. Often, with non-oncology programs, we can start with healthy volunteer studies where we establish a full pharmacokinetic/pharmacodynamic (PK/PD) and safety analysis upfront in our first-time-in-human (FTIH) trial before we move to populations of special interest. With oncology trials, we establish the safety of where we want to begin our dosing based on our animal trials in our pre-clinical package, and we move directly into patients.

With our FTIH, we will do an initial PK draw to see if the dosing is at the levels we expect it to be at. We’ll save the full comprehensive package until proof of concept is shown because that will reduce unnecessary risk and prevent premature investments. The full PK package for oncology studies can include drug-drug interaction studies and studies of patient special populations with patients with dysfunctional kidneys or livers. We can also go into food effects with high-fat and low-fat meals. We may also do a definitive QT study, depending on what the pre-clinical work showed.

If you have any questions about how to build your PK package or where you should start with your dosing, please feel free to contact D2V Clinical today.

I’m Dr. Vijay Reddy, the Chief Medical Officer of D2V Clinical. I am licensed physician in the United States, and I’ve worked in the biopharmaceutical industry for many years.

My career in antibody drug conjugates (ADCs) began many years ago while doing my Ph.D. when I developed monoclonal antibodies that were conjugated with the chemotherapeutic drug Doxorubicin that targeted CEA expressing colorectal cancer cells.

Advances in ADC design and technology have rapidly increased the pace of approvals in recent years with over a dozen ADCs that have been approved and many more on the way. ADCs are designed to combine the benefits of targeted therapy and chemotherapy. The three components of ADCs to remember broadly are the vehicles which are the monoclonal antibodies that deliver what’s called a payload of chemotherapeutic drug to the cancer cells that have a target, which is a tumor- associated antigen.

Early-phase clinical research lays the foundation for the success of ADCs, and careful evaluation has to be given to the target identification, patient selection, safety, and dose optimization for efficacy. The best example to understand how critical the early-phase development is can be understood by the development of the first ADC that was approved, gemtuzumab ozogamicin or Myelotarg for acute myeloid leukemia.

While it was originally approved nearly 20 years ago, it was subsequently withdrawn voluntarily due to safety issues. However, after further dose optimization – with a lower dose and different scheduling, it was found that the benefit outweighed the risk, and the FDA approved it 17 years after its initial execrated approval. Therefore, early-phase clinical development is critical in understanding the target. For example, certain targets such as CD30 are ubiquitously expressed by cancer cells, in the case of Hodgkin’s Lymphoma here with Brentuximab.

In the case of HER2, ADCs targeting HER2, 15%-20% of breast cancer cells express this and can also be, however, effective in a so-called bystander effect where HER2 null-cells, which have no HER2 expression, can benefit. Therefore, understanding the payload and the target are critically important.

The recent ASCO conference demonstrated promising results for several ADCs that are being evaluated in clinical trials. Examples of these ADCs include targets such as B7H3 in metastatic castration resistant prostate cancer, HER3 in metastatic breast cancer, TROP-2, HER3, MET, CEACAM5, etc. in NSCL lung cancer.

In conclusion, ADCs are antibody drug conjugates that combine the benefits of antibodies and targeted therapy with chemotherapy, or such toxic agents. Early phase ADC clinical development is a dynamic process and is driven by dedicated professionals like you. If you’re working with an ADC development program and require expert guidance, we are here to help.

Contact D2V Clinical today to schedule a consultation and talk to our experts regarding your ADC development program.