Abstract
Background: Zelenectide pevedotin (zele, formerly BT8009) is a Bicycle® Toxin Conjugate (BTC®) comprised of a bicyclic peptide targeting Nectin-4 conjugated to MMAE. NECTIN4 amp has been shown to be a predictive biomarker for response to enfortumab vedotin in metastatic urothelial cancer (Klümper et al., 2024), and this post-hoc analysis assesses the utility of NECTIN4 amp as a predictor of zele
response in NSCLC pts.
Methods: Zele is being evaluated in the ongoing Ph 1/2 study BT8009
100/Duravelo-1 (NCT04561362) for safety and efficacy in pts with advanced solid tumors associated with Nectin-4 expression. This analysis focuses on NSCLC pts who had baseline tissue samples available to test for NECTIN4 amp by fluorescence in-situ hybridization. NECTIN4 amp was defined as a ratio of NECTIN4:CEN1 of ≥2.0. Anti-tumor activity was assessed per RECIST v1.1 by investigator.
Results: As of 13 Sep 2024, 40 heavily pretreated pts with NSCLC were enrolled. At baseline, NSCLC pts had a median age of 63.5 (34–80), median prior lines of therapy of 3 (1–8), and ECOG of 0 (25%) or 1 (75% each). Twenty-nine pts with NSCLC from dose escalation/expansion and treated with a starting dose of 5 mg/m2 or higher were efficacy evaluable; 3 achieved partial response (PR) resulting in an ORR of 10.3%. Seventeen pts were tested for NECTIN4 amp, of those, 6 were positive (35.3%), and 5 of them were efficacy evaluable. Of these, 2
achieved a confirmed PR with an ORR of 40.0% (5.3, 85.3), and the remaining 3 had stable disease (disease control rate 100.0%). Of the NECTIN4 non-amp pts, 8 were efficacy evaluable and none had a response. Safety and tolerability of zele in the NSCLC population was similar to a previously reported cohort of bladder cancer pts (Reig et al., 2024). Fatigue, nausea, and diarrhea were the most common AEs. Grade ≥3 zele-related adverse events (AE) occurred in 37.5% of pts, and Grade ≥3 zele-related serious adverse events occurred in 12.5% of pts.
Conclusions: NECTIN4 amplification appears to show predictive clinical utility in identifying NSCLC pts with enhanced response to zelenectide pevedotin, with an ORR of 40.0% in NECTIN4 amp NSCLC pts. Further exploration of zele and NECTIN4 amp stratification strategies in NSCLC pts is warranted. Clinical trial ident
response in NSCLC pts.
Methods: Zele is being evaluated in the ongoing Ph 1/2 study BT8009
100/Duravelo-1 (NCT04561362) for safety and efficacy in pts with advanced solid tumors associated with Nectin-4 expression. This analysis focuses on NSCLC pts who had baseline tissue samples available to test for NECTIN4 amp by fluorescence in-situ hybridization. NECTIN4 amp was defined as a ratio of NECTIN4:CEN1 of ≥2.0. Anti-tumor activity was assessed per RECIST v1.1 by investigator.
Results: As of 13 Sep 2024, 40 heavily pretreated pts with NSCLC were enrolled. At baseline, NSCLC pts had a median age of 63.5 (34–80), median prior lines of therapy of 3 (1–8), and ECOG of 0 (25%) or 1 (75% each). Twenty-nine pts with NSCLC from dose escalation/expansion and treated with a starting dose of 5 mg/m2 or higher were efficacy evaluable; 3 achieved partial response (PR) resulting in an ORR of 10.3%. Seventeen pts were tested for NECTIN4 amp, of those, 6 were positive (35.3%), and 5 of them were efficacy evaluable. Of these, 2
achieved a confirmed PR with an ORR of 40.0% (5.3, 85.3), and the remaining 3 had stable disease (disease control rate 100.0%). Of the NECTIN4 non-amp pts, 8 were efficacy evaluable and none had a response. Safety and tolerability of zele in the NSCLC population was similar to a previously reported cohort of bladder cancer pts (Reig et al., 2024). Fatigue, nausea, and diarrhea were the most common AEs. Grade ≥3 zele-related adverse events (AE) occurred in 37.5% of pts, and Grade ≥3 zele-related serious adverse events occurred in 12.5% of pts.
Conclusions: NECTIN4 amplification appears to show predictive clinical utility in identifying NSCLC pts with enhanced response to zelenectide pevedotin, with an ORR of 40.0% in NECTIN4 amp NSCLC pts. Further exploration of zele and NECTIN4 amp stratification strategies in NSCLC pts is warranted. Clinical trial ident
| Original language | English |
|---|---|
| Pages | S69-S71 |
| DOIs | |
| Publication status | E-pub ahead of print - 29 Mar 2025 |
| Event | European Lung Cancer Congress (ELCC) 2025 - Paris, France Duration: 26 Mar 2025 → 29 Mar 2026 |
Conference
| Conference | European Lung Cancer Congress (ELCC) 2025 |
|---|---|
| Country/Territory | France |
| City | Paris |
| Period | 26/03/25 → 29/03/26 |
