Data from a novel Nectin-4 ADC trial showed zero responses in patients with prior topoisomerase therapy. This strongly suggests that payload resistance, not just the ADC target, is a critical mechanism that will dictate future treatment sequencing.

A "tsunami" of antibody-drug conjugates (ADCs) are in development for ovarian cancer, but many share the same TOP1 inhibitor payload. This creates a significant future clinical challenge: after a patient progresses on one such ADC, it is unknown if another with the same payload will be effective, creating an urgent need for sequencing data.

Sequencing antibody-drug conjugates (ADCs) like enfortumab vedotin (EV) and disitamab vedotin is complicated because both use the same MMAE cytotoxic payload. If a tumor develops resistance to the MMAE from EV, it is unlikely to respond to a subsequent ADC using the same payload.

As numerous antibody-drug conjugates (ADCs) move to frontline cancer therapy, a key concern emerges: most use a small number of payloads (like topo-1 inhibitors). There is pessimism about whether sequencing different ADCs that share the same payload will be effective.

Retrospective data shows that using one Antibody-Drug Conjugate (ADC) after another, particularly those with the same class of payload like TOP1 inhibitors, results in a low response rate of 10-20%. This creates a significant unmet need and a major clinical challenge for patients who progress on a first-line ADC.

Most new antibody-drug conjugates (ADCs) for ovarian cancer use the same topoisomerase-1 (Topo1) inhibitor payload. This similarity will likely prevent their sequential use due to cross-resistance, forcing clinicians into a "one-shot" scenario where they must choose the single best Topo1-based ADC upfront for a patient.

With 18 of 19 ADCs in development for SCLC using a topoisomerase-1 inhibitor payload, there's a significant risk that patients may not respond to a second ADC after progressing on a first. This highlights a critical need to develop ADCs with alternative payloads to provide more therapeutic options and overcome resistance.

As more antibody-drug conjugates (ADCs) become available, a key concern is resistance to the cytotoxic payload. If a tumor develops resistance to a topoisomerase-1 inhibitor from one ADC, it may not respond to other ADCs using the same payload, regardless of their different antibody targets, complicating future treatment sequencing.

When patients progress on an antibody-drug conjugate (ADC), the resistance is frequently due to the tumor becoming resistant to the chemotherapy payload (e.g., a topoisomerase inhibitor). This is more common than the tumor losing the surface target, which critically impacts the sequencing of subsequent ADCs.