The Harmony VI lung cancer trial's confusing inclusion/exclusion criteria for high-risk patients highlights a critical debate: developing drugs in idealized settings can limit their applicability and create uncertainty for treating the actual patients clinicians see daily.
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.
Unprecedented response rates (up to 72% in HER2 3+) for new ADCs in Phase 1/2 endometrial cancer trials are challenging the historical view of early trials as having low success. This shift encourages earlier patient enrollment in targeted therapy studies.
Emerging data in urothelial cancer suggests a potential solution to the ADC sequencing problem. After treatment with a Nectin-4 targeted ADC, using a second Nectin-4 ADC with a different payload (topo-1 inhibitor instead of MMAE) still demonstrated efficacy.