1310P - SHR-A1921: A trophoblast cell-surface antigen 2 (TROP-2) targeted antibody-drug conjugate (ADC) for the treatment of advanced NSCLC

Background

SHR-A1921 is a novel ADC composed of a humanized anti-TROP-2 IgG1 mAb attached to a DNA topoisomerase I inhibitor via a tetrapeptide-based cleavable linker. Here we reported the clinical activity and safety of SHR-A1921 in patients (pts) with locally advanced and metastatic NSCLC.

Methods

This was a first-in-human, dose-escalation, dose-expansion, and efficacy-expansion phase 1 study. In NSCLC expansion cohort, pts with or without actionable oncogenic alterations (AGAs) who had failed standard of treatment were enrolled to receive SHR-A1921 at 3.0 mg/kg Q3W until progression or unacceptable toxicity.

Results

As of Feb 19, 2024, 54 pts were enrolled, comprising 33 (61.1%) without AGAs and 21 (38.9%) with AGAs. 33 (61.1%) pts were diagnosed with non-squamous NSCLC, 20 (37.0%) with squamous NSCLC, and the pathology of 1 (1.9%) pt remaining unknown. 22 (40.7%) pts had received ≥3 prior lines of therapy. Among the 33 pts without AGAs, 32 (97.0%) had been treated with anti-PD-1/PD-L1 antibodies, and all had failed platinum-based chemo. All the 21 pts with AGAs harbored EGFR mutations and had received prior 3^rd TKI and platinum-based chemo. Median follow-up was 10.0 mo (range 0.4-21.2). Among the 49 response-evaluable pts, the ORR was 22.4% (95% CI 13.0-35.9), and median DoR was 10.8 mo (95% CI 4.1-not reached). Median PFS was 5.7 mo (95% CI 4.1-8.3), and median OS was not matured. SHR-A1921 was effective in both non-squamous and squamous NSCLC pts (Table). 19 (35.2%) pts experienced grade 3 or 4 treatment-related adverse events (TRAEs), with the most common being stomatitis (9.3%). No TRAEs led to death. One (1.9%) grade 3 drug-related interstitial lung disease was observed and led to treatment discontinuation.

Conclusions

SHR-A1921 showed promising clinical activity and a manageable safety profile in heavily pretreated NSCLC pts. A phase 3 study of SHR-A1921 in pts with advanced non-squamous NSCLC have been planned. Table: 1310P

Efficacy summary

BOR, ORR, DCR and DoR were analyzed in treated pts evaluable for anti-tumor response. PFS was analyzed in all treated pts.

Clinical trial identification

NCT05154604.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

Y. Wu, Z. Lin, Z. Zhang, S. Wang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.