Abstract 656MO
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
BTC (N=22) | UC (N=23) | GC/GEJA (N=13) | CRC (N=14) | Other tumors (N=26) | |
ORR*, n/N (%)(95% CI) | 9/15 (60.0%)(32.3–83.7) | 13/22 (59.1%)(36.4–79.3) | 6/12 (50.0%)(21.1–78.9) | 4/11 (36.4%)(10.9–69.2) | 7/25 (28.0%)(12.1–49.4) |
HER2 IHC 3+ | 7/10 (70.0%) (34.8–93.3) | 2/6 (33.3%) (4.3–77.7) | 4/10 (40.0%) (12.2–73.8) | 3/3 (100.0%) (29.2–100.0) | 4/8 (50.0%) (15.7–84.3) |
HER2 IHC 2+ | 0/1 | 7/10 (70.0%) (34.8–93.3) | 2/2 (100.0%) (15.8–100.0) | 0/3 | 1/8 (12.5%) (0.3–52.7) |
HER2 IHC 1+ | 1/2 (50.0%) (1.3–98.7) | 4/5 (80.0%) (28.4–99.5) | 0 | 0/1 | 2/6 (33.3%) (4.3–77.7) |
HER2 mutation and/or amplification | 1/2 (50.0%) (1.3–98.7) | 0/1 | 0 | 1/4 (25.0%) (0.6–80.6) | 0/3 |
*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.
Resources from the same session
Invited Discussant LBA35, 661MO and 662MO
Presenter: Philippe Cassier
Session: Mini oral session - Developmental therapeutics
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