The Role of Biomarkers in Immuno Oncology CRO Clinical Trials

Biomarkers or biological markers are molecules which indicate normal or abnormal processes within the body. They are found in blood, urine, stool, other bodily fluids and tissues.

In cancer, biomarkers can include substances which are produced by cancer tissues or by other cells which react to cancer in the body. Biomarkers can be helpful in detecting, diagnosing and predicting responses to therapy. It also assists with tracking results of treatment or cancer growth as well as determining whether the cancer has returned following remission.

There are three main tests involving biomarkers, namely:

1. Genetic – involves searching for mutations and abnormal changes which include missing, extra, or incorrectly placed genes.
2. Biochemical – determines if there are too many proteins or if proteins are overactive.
3. Chromosome – identifies abnormal changes within chromosomes.

Drawing Focus on Individuals in Immuno Oncology CRO Clinical Trials

Biomarkers allow Immuno Oncology Contract Research Organization Clinical Trials to focus on an individual's unique characteristics. These help researchers and health care professionals improve the support provided to patients by understanding how to prevent different diseases, diagnosing the severity or stage of an illness, helping to inform a patient with treatment options and determining the likelihood that the disease will return.

The identification of biomarkers and continuing discovery of new ones mark the evolution of how clinicians and patients can effectively determine personalised treatments.

Biomarkers can include a variety of signals that could be T-cell like immune cell activity function such as proliferation. It also helps in looking at tumour mutations because tumour cells keep changing their genomic information. Biomarkers can give us very important insights for what outlook a typical cancer will be.

Details of molecular pathways like metabolism, biochemical reactions, and the ability to measure certain protein levels in our blood to see how its changes in our system predict the clinical status of cancer patients. So basically biomarkers can be applied to all cancers. They are needed to learn more about the disease, to identify therapeutic targets and to help cancer patients to survive.

Two Approaches to Using Biomarkers in Immuno Oncology CRO Clinical Trials

Essentially there are two ways of looking at biomarkers in Oncology clinical trials. On the one hand, biomarkers demonstrate if a particular therapeutic modality has any kind of pharmacological effect during the clinical trial. The other way is to determine which patients are most likely to respond to a particular therapy.

In general, biomarkers are very specific to their target receptors. For instance, in determining whether it has a pharmacological effect, an investigator may be looking to see if a drug inhibits its target. For instance, does the drug hit a particular enzyme and at what concentration does it hit that particular enzyme.

The other side of the equation is implementing a personalised approach to medicine or precision-type medical approach where people are selected based on who is most likely to respond.

In oncology, either the tumour or blood is tested to evaluate whether a particular cancer has a mutation that might be amenable to treatment. This could lead to the selection of a drug that specifically targets that mutation. This is how a biomarker can be used to select patients who are most likely to respond.

How Biomarkers Can Be Integrated Into Immuno Oncology CRO Clinical Trials

Essentially, there are two ways in which a biomarker can be integrated into an Immuno Oncology CRO trial.

A genome-wide association study can be used for identifying a biomarker signature which corresponds to a robust drug response. This is an indirect approach which does not depend on known biology which associates signatures to the drug’s MOA. As such, this approach has less of a chance to deliver value to the pharma company.

The second approach is more preferable for oncology drugs and is directly linked to the drug’s mechanism of action. The biomarker could also be the drug being targeted. Examples are EGFR, HER2 inhibitors.

In some other cases, the biomarker can identify other proteins in the activation pathway of the drug. In this case, the alteration will enable the tumour to escape the effect of the drug.

In either of these cases, a correlation of biomarker measurement with the drug activity is determined through nonclinical studies. This is followed by a preliminary assessment in early Immuno-oncology studies.

Once the pharma company has this data, they can design and execute pivotal trials by using a clinical trial assay which includes or excludes patients based on biomarker measurement which indicates a likely drug response.

In turn, this establishes a basis for the expectation of an enhanced value through a higher probability of success of the Immuno-oncology trials.

Mitigating Risk Revenue Optimisation in Oncology CRO Clinical Trials

When incorporating biomarker stratification in drug development, large pharma companies dislike potentially excluding patients who may derive benefit from the population being treated. Since individual cancers can have multiple triggers or be generated through tumour evolution, targeting a single biomarker is not the perfect predictor of initial or durable response.

To reduce the risk of non-response a high cut-off can be set for the biomarker. However, this could come at the price of excluding some responders from the group being treated. This kind of outcome is undesirable for the pharma company whose goal is to ensure the most effective treatment is delivered to every patient.

Pharma companies have utilised two methods to meet this challenge. In the first method, they adopt a very low cut-off for the biomarker measurement so as to exclude the least number of potential patients. This approach can be successful when in situations where previous studies have indicated that many patients respond strongly to the drug treatment.

The other strategy which some pharma companies adopt is to enrol a broad population in the oncology CRO clinical trial but perform an adequate biomarker-based analysis of the subgroup.

This approach could lead to approval based on an analysis of the sub-group if the primary endpoint isn’t achieved in the broader population.

Since trials in an unstratified population tend to be bigger than the ones using a biomarker-guided enrollment, such an approach requires a larger investment in clinical development. However, it significantly enhances value by increasing the likelihood of trial success and concomitantly preserving the possibility of its utilisation for the larger population.