ADC Sequencing studies

Sun Yat-sen University

A China-only, retrospective ISS study evaluating optimal ADC sequencing in HER2-low (IHC 1+/2+ and FISH-) BC has been listed (N=700, SSD: Jan 2020, PCD/SCD: Jan 2026)

• The study is a retrospective analysis of clinical data from HER2-low BC patients treated with sequential ADCs
• Cohorts include (ADC1, ADC2)
  • Trastuzumab deruxtecan (T-DXd, Enhertu, HER2-ADC), Trodelvy
  • Trodelvy, T-DXd
  • Disitamab vedotin (RC48; HER2-ADC), T-DXd
  • T-DXd, RC48
  • Sacituzumab tirumotecan (sac-TMT, SKB264, MK-2870; TROP2-ADC), T-DXd
  • Trastuzumab emtansine (Kadcyla; HER2-ADC), TQB2102 (HER2-ADC)
  • TQB2102, T-DXd
  • RC48, TQB2102
• The study aims to evaluate efficacy and safety profiles of various ADC combinations, including PFS as the primary endpoint and OS as a secondary endpoint
  • Genomic profiling and routine clinical data will also be leveraged to identify potential prognostic biomarkers and elucidate pathways involved in ADC resistance

University of California

A new observational, prospective ISS ENCORE study to collect real-world data to evaluate impact of ADC sequencing in HR+/HER2- mBC or mTNBC has been listed (N=100; PCD/SCD: Dec 31, 2030)

• Gilead is listed as a collaborator for this study
• Primary endpoints include rwPFS of first ADC (ADC1) and rwPFS of second ADC (ADC2)
• Secondary endpoints include DOR, ORR, DCR, best overall response (BOR), rwOS, and AEs 
• Participants will have medical chart reviews and biospecimens collected for the duration of the routine care with ADC1 and/or ADC2
• After the last dose of ADC2, participants will continue to be followed for survival data collection via chart review every 12 weeks for up to 2 years
• The study will have 4 cohorts:
  • HR+/HER2- mBC (cohort 1) or mTNBC (cohort 2) patients with plans to start an FDA-approved ADC as first ADC therapy
    • If a patient enrolls on a clinical trial of an experimental therapy after ADC1, they will be taken off the study
  • HR+/HER2- mBC (cohort 3) or mTNBC (cohort 4) patients with plans to start an FDA-approved ADC as second ADC therapy
    • Patients who received an FDA-approved ADC as their first ADC as monotherapy will be able to participate in cohorts 3 and 4 
• The trial excludes patients who have received an experimental ADC in the metastatic setting or those currently participating in a clinical trial with an ADC
• Collection of more real-world data may provide additional insight into optimal ADC sequencing that has thus far been inconclusive