Exploring the Future of Oncology with ADCs and TILs: Key Insights From ASCO  

The 2024 ASCO Annual Meeting from the American Society of Clinical Oncology is a fantastic platform for clinical researchers to discuss the latest advancements and challenges in oncology research. Worldwide Clinical Trials attends each year to hear from the research community, connect with our sponsors and sites, and explore potential partnerships to drive forward novel treatments.

This year, Matt Cooper, PhD, our Executive Director, Therapeutic Strategy Lead, Oncology, attended and found the presentations around antibody-drug conjugates (ADCs) and tumor-infiltrating lymphocytes (TILs) to be of great interest to the future of oncology therapeutics. Both offer significant treatment potential and have received recent approvals, but both face obstacles that have, to date, limited their expansion more widely into different tumor settings.

Antibody-Drug Conjugates: Advancing Precision Therapy

ADCs represent a compelling combination of targeted antibody therapy and potent chemotherapy, aiming to enhance treatment efficacy while minimizing systemic toxicity. Currently, there are 12 approved ADC drugs, and several hundred more are in the development pipeline. Four distinct challenges were discussed at ASCO involving ADC development, including:

  1. Target Expression Levels: The targeted antigen must be sufficiently expressed on tumor cells.
  2. Toxicity Management: It’s critical to balance on-target with off-target toxicity to prioritize patient safety.
  3. Linker Stability: The stability of the linker, which attaches the chemotherapy agent to the antibody, is essential for efficient and precise drug-delivery.
  4. Biomarker Development: Identifying predictive biomarkers can help classify patients based on safety and efficacy profiles.

Researchers are actively looking for ways to solve these problems with the goal of finding the optimal balance between efficacy and toxicity for many of these drugs. ADCs are continually evolving, bringing forward new targets across various cancer types, including rare and orphan cancers.

Although there are a range of efficacies across different tumor types that require a greater understanding, the use of circulating tumor DNA profiles holds promise for personalized treatment strategies that better target the drug for the patient, potentially revolutionizing how ADCs are deployed in clinical practice.

Tumor-Infiltrating Lymphocytes: Harnessing the Power of the Immune System

The recent approval of the first TIL therapy for melanoma marked a significant milestone in the field of immunotherapy. Previously, T-cell therapies had been primarily used on liquid tumors, as the T-cells were unable to penetrate the solid tumor environment. Unlike CAR T therapies, TILs are produced in vitro by purifying natural infiltrating lymphocytes from the patient’s own tumor microenvironment. While this approach bypasses some of the complexities associated with CAR T’s genetic modification, TIL therapy is still a multifaceted procedure to deliver, requiring a multidisciplinary team of a surgeon, oncologist, and hematologist.

Its primary challenges include:

  • Production Delays: The time-intensive process of expanding TILs to therapeutic quantities poses logistical hurdles.
  • Response Rates: To date, approximately 30% of patients are achieving objective responses, indicating considerable room for improvement.
  • Microenvironment Management: Optimizing the tumor microenvironment to enhance TIL efficacy remains a critical focus of research efforts.
  • Toxicity Considerations: High doses of IL-2 are required to stimulate T-cell growth and survival and it is given alongside the TIL infusion, leading to significant side effects in many patients.

Clinical researchers are currently working to streamline TIL production and enhance treatment outcomes by more efficiently regulating immune responses — such as combination therapy with checkpoint inhibitors.

Post-ASCO 2024: Paving the Way Forward

Matt Cooper’s takeaways from the 2024 ASCO Annual Meeting underscore the dynamic landscape in oncology, with precision medicine and immunotherapy converging to offer new treatment solutions. Both ADCs and TILs are promising ways forward to transform cancer care by targeting tumors more effectively while reducing adverse effects, representing an exciting time in clinical research. As studies continue to unravel the complexities of these therapies, collaboration across multidisciplinary teams will play a pivotal role.

Interested in hearing more insights from Matt? Check out this webinar on navigating the landscape of oncology clinical trials.

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