ADC-based Oncology Clinical Trials: Monitoring ILD Toxicities to Meet Regulators’ Expectations

Advances in oncology precision medicine and therapy have increased the number of immune therapies and molecular-targeted agents for the treatment of most solid tumors. Antibody Drug Conjugates (ADCs) are one of the fastest-growing classes of cancer drugs in clinical development and have the potential to change the management of cancer patients in the clinic.

ADC construct typically involves a monoclonal antibody (mAb) covalently attached to a cytotoxic drug via a chemical linker. This chemical construction gives ADCs two advantages:

• Highly specific/accurate targeting ability
• Efficient lysis of cancer cells

Unfortunately, ADCs have been associated with the risk of pulmonary abnormalities, the most concerning of which is Drug-induced Interstitial Lung Disease (DI-ILD). DIILD is the term used to define a subset of ILD resulting from exposure to pharmaceutical drugs causing interstitial inflammation and possibly interstitial fibrosis.

As a result, in clinical trials investigating ADCs for the treatment of cancers, regulatory agencies around the world are asking trial sponsors to monitor for ILD toxicity. Research has shown that early detection, diagnosis, and management can prevent the worsening of ILD in these patients since in many cases the complications are reversible.

However, diagnosis of ILD in ADC clinical trials requires proactive longitudinal monitoring of subject health using clinical, laboratory, and radiology tools and no single tool can provide a definite diagnosis. Radiology methods such as High-Resolution Computed Tomography (HRCT) is the gold standard for the detection and characterization of ILD and, when combined with clinical and laboratory data, provides a powerful method for the accurate diagnosis of DIILD.

Integration of radiology data with clinical and laboratory tests such as pulmonary function tests and review of this information by a centralized independent joint events committee consisting of expert clinicians provides a consistent and standardized way to adjudicate DIILD cases.

Perceptive Imaging is actively supporting numerous clinical trials of ADC-based treatments and working with global trial sponsors to ensure their protocols support patient safety and meet regulators’ evolving expectations.