656MO - The HER2-targeting ADC SHR-A1811 in HER2-expressing/mutated advanced non-breast solid tumors (STs): Results from the global phase I study

Background

SHR-A1811 is a novel ADC composed of trastuzumab (anti-HER2), a cleavable linker, and a topoisomerase I inhibitor payload, with optimized drug-antibody ratio of 6 and strong bystander killing effect. We initiated this global, dose escalation, PK expansion, and indication expansion phase 1 study in HER2-expressing/mutated advanced STs. The primary analysis showed that SHR-A1811 was well-tolerated and had promising antitumor activity, especially in HER2-positive or low-expressing breast cancer ( AACR 2023 , CT175). Here we report the findings focusing on non-breast STs.

Methods

Patients (pts) with advanced, unresectable, or metastatic HER2-expressing/mutated STs that were refractory or intolerant to standard therapies were treated with SHR-A1811 at 1.0–8.0 mg/kg Q3W (IV).

Results

As of Feb 28, 2023, 98 pts with non-breast STs were enrolled. Pts had a median 2 prior lines of therapy (range 1–9), and 66.3% had ≥2. ORR was 45.9% (39/85 evaluable pts; 95% CI 35.0–57.0); DCR was 88.2% (75/85; 95% CI 79.4–94.2); and median TTR was 1.4 mo (range 0.7–5.8). ORR was 54.1% (20/37) in pts with HER2 IHC3+, 41.7% (10/24) with IHC2+, and 50.0% (7/14) with IHC1+. For individual tumor type, ORR was 56.3% (9/16) in BTC pts, 59.1% (13/22) in UC, 50.0% (6/12) in GC/GEJA, and 36.4% (4/11) in CRC (data by HER2 status for each tumor type are shown in table). Overall, 38 (38.8%) of 98 pts had disease progression or died; the 6-mo PFS rate was 52.1%. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 50 (51.0%) of pts; the most common (≥10%) were decreased neutrophil count and anemia. Serious TRAEs were reported in 15 (15.3%) pts. Of note, only 1 (1.0%) pt had interstitial lung disease. Table: 656MO

ORR by tumor type and HER2 status

*tumor response evaluable set.

Conclusions

SHR-A1811 had favorable antitumor activity and acceptable safety profile in heavily pretreated HER2-expressing/mutated advanced non-breast STs, including BTC, UC, GC/GEJA, and CRC.

Clinical trial identification

NCT04446260, Release date: 24 June 2020.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals.

Funding

Jiangsu Hengrui Pharmaceuticals.

Disclosure

K. Liu, S. Gu: Financial Interests, Institutional, Funding: Jiangsu Hengrui Pharmaceuticals. S. Rong: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.