Identifying and Pursuing Optimization of ADC Treatment in Cancer

Commentary
Video

Antibody-drug conjugates are effective, but strategies such as better understanding the mechanisms of action may lead to enhanced care for patients with cancer.

At the 16th Annual World ADC Summit in San Diego, CA, Aditya Bardia, MD, MPH, FASCO, delivered a presentation titled “Reviewing the ADC Clinical & Approval Landscape: What Direction are ADCs Heading to Reshape Frontline Oncology Treatments For Patients?”.

Antibody-drug conjugates (ADCs) work, according to Bardia, but there are still obstacles that need to be circumvented to make them as optimal as possible for patients. Some of the solutions, briefly, included identifying biomarkers, proper ADC sequencing strategies, and optimal toxicity-management strategies.

Further understanding the mechanisms of resistance of the ADC and whether they’re payload-driven or antibody-driven was another consideration that Bardia highlighted, when prompted on the patient-resistance mechanisms that various cancers have and the way they affect long-term care with ADCs.

Looking towards the future, he expressed excitement regarding the possibility of combining ADCs with other modalities of treatment; immunotherapy plus ADCs was one example of a combination that he highlighted.

Bardia is a professor in the department of medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the University of California Los Angeles Health Jonsson Comprehensive Cancer Center.

Transcript:

At the World ADC Conference, I presented clinical updates related to [ADCs], the development of TROP2 ADCs, HER2 ADCs, and the upcoming ADCs, but then we focused on the potential challenges related to the ADCs, and strategies to overcome those challenges, including biomarkers, ADC sequencing, management of toxicities related to ADCs, and also building ADC-based combinations.

These [ADCs] work. They’re able to control the disease, but eventually, we see disease progression. Understanding the mechanism of resistance—is it more payload-driven or more antibody-driven—is something else that would be important. We can prolong the duration that a patient is on an effective therapy, and that can also guide ADC-based sequencing.

From an ADC perspective, I’m excited about combinations. Particularly in combination with immunotherapy, we’re seeing better results than what we’ve seen with ADCs alone. I’m also excited about ADC-based combinations that leverage the payload because that could improve synergy and further lead to better outcomes for patients.

Reference

Bardia A. Moving forward with ADCs in clinic: challenges and opportunities. Presented at the 2025 World Antibody Drug Conjugate Conference; San Diego, CA; November 3-6, 2025.

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