A Reason to Hope: Overcoming Treatment Challenges for Lung Cancer with ADCs
Surpassing the mortality rates associated with both prostate and breast cancer; the number of global lung cancer diagnoses now exceeds 2 million affected persons. Lung cancer is a worldwide leader in oncological-related incidences and mortalities. In 2023, approximately 238,340 individuals in the United States will be diagnosed with lung cancer. However, revolutionary advances in precision medicine are giving those affected a dose of much-needed hope.
Precision medicine is the practice of applying genetics, molecular, and lifestyle profiling to aid in determining a customized approach to treating individual patients. Using precision medicine principles as a guide, research scientists developed novel methodologies using antibodies to combat oncological conditions. Subsequently, harnessing the targeting power of antibody-drug conjugates (ADCs) offers a newly explored gateway to finding more efficacious treatment prospects for advanced late-stage cancers.
Treating lung cancer is challenging because of its late detection due to symptom crossover and masking. Late-stage diagnoses are more common in elderly people and often present with advanced tumor progression that allows for very few viable treatment options. Understanding these obstacles makes the potential of using ADCs in an adjunctive capacity with other biologics a noteworthy approach for treating lung cancer. CROs globally are highly anticipating a huge influx of new lung cancer trials in this space.
Understanding Antibody-Drug Conjugates
What are ADCs?
Antibody-drug conjugates (ADCs) represent a revolutionary wave of modern treatment approaches. Touted as a sort of biologic missile within the clinical community, ADCs use the specific targeting power of an antibody paired with potent cytotoxic biologics (cancer lysing chemicals aka chemotherapy) to cleave onto the surface antigen of cancer cells.
Once linked, the potent payload can deliver the concentrated cancer lysing cocktail to the tumorous cell act. Penetrating the tumor cell using ADCs demonstrates the ability to shrink tumors more effectively in clinical studies. More impressively, the use of ADCs broadens what is possible in terms of efficacy because of their cellular trafficking and internalization abilities.
ADCs Paired with Adjunctive Treatment Strategies Offers Greater Efficacy Than Chemotherapy Alone
As a standalone treatment, chemotherapy demonstrates less therapeutic benefit than the use of targeted therapies. ADCs are also far more effective at preserving healthy cells with the added benefit of lower toxicity levels resulting in above-average tolerability. Patient tolerability is strategic in helping them receive the full duration of available treatments without unacceptable complications.
Additional notable advantages associated with the use of ADCs for the treatment of lung cancer include:
- Patient exposure to excessive amounts of systemic chemotherapy agents is reduced.
- The bystander effect allows for greater impact towards the tumor environment.
- Internalization and intracellular trafficking of the ADC allows for greater tumor penetration.
ADCs Exceed Efficacy Expectations in Clinical Studies by Demonstrating the Ability to Impact the Tumor Microenvironment
Bioengineering customized payloads towards more resistance areas within the tumor microenvironment (TME) allows for newly realized opportunities in precision medicine. Designing specific linkers to the antibodies allows for precise targeting into specific cell-types housed within the TME. The TME features a complex ecosystem that is also capable of inciting tumor activity.
The TME is comprised of a web-like intracellular matrix, consisting of signaling molecules, fibroblasts, stromal, immune, and blood cells, making it difficult to optimize treatment. Finding effective strategies to treat the entire scope of a cancer-affected environment (liposomal, hematologic, and solid tumors) is challenging, yet ADCs provide researchers with this rare mechanistic opportunity.
Navigating Unique Challenges Associated with Using ADCs in Oncological Treatment Approaches
As the number of global ADC approvals continues to rise, sparking more diverse clinical trials, we can expect more in-depth information. Through interdisciplinary applications, ADCs continue to shed more light regarding their unique mechanism of action (MOA). The current pharmacokinetic values and safety profiles for the approved ADCs are still being explored through vast clinical studies and application models. However, there is conclusive evidence highlighting the unique obstacles presented by ADCs in clinical trials. Many of the findings indicated challenges related to:
Payload Potency and Diversity
Establishing safe levels of payload potency seems to represent one of the more significant challenges with ADCs. Due to their larger size, they are significantly more potent than their small molecule therapeutic counterparts. As a larger molecule, the ADC harbors pharmacokinetic factors that present variable half-lives and inconsistent circulation. Experts suggest finding a balance hinges on the final concentration of the tumor payload values. Further mitigation of toxicities may rest in bi-specific antigen selection and advances in the development of multi-binding antibodies.
Overcoming Drug Resistance
The characterization of ADCs and their relationship to tumor activity is still under study. What we do know is that some tumors escape the impact of the ADCs in a myriad of ways that are not fully understood. Clinical evidence suggests that tumor activity can evade ADC targeting by reducing the expression levels of antigens and choosing alternate intracellular pathways as an escape mechanism. However, it is not yet clear on the exact interaction between the conjugate and the antigen.
Novel ADC Payloads: The Next Wave of Clinical Trials
There are over 100 active ADCs in clinical trials globally. The landscape of ADCs as a treatment platform is evolving quickly, and industry experts speculate on what ADC-expanded technologies may look like in the next few years. A great deal of momentum has also been initiated toward an understanding of how to circumnavigate tumor escape mechanisms. Other probable future developments could feature the enhancements of existing novel ADC payloads, such as those that demonstrate an amplified antitumor immune response.
The future developmental prospects of ADC-specific research are exciting to many. Advances in biochemical engineering will provide solutions for some of our toughest health concerns. One way to explore the exciting future prospects of ADC-specific research is through oncology clinical trials. Clinical study processes can yield valuable insights, but they come with significant stakes. That’s why CROs are stepping in to help, and the Vial Oncology CRO is a standout example. This CRO is powered by cutting-edge technology that streamlines processes, reduces enrollment periods, and enables faster startup and consolidated site activation. With fixed-pricing agreements and multifaceted clinical trial execution across oncology indications and phases, the Vial Oncology CRO is helping biotech sponsors achieve lightning-fast results.
Trusted by leading sponsors, Vial draws from its vast experience as a top-tier CRO to achieve 90%+ site activation within 30 days. Contact one of our team members for more information on how to run faster, better, and cheaper clinical trials with Vial CRO!