SHR-A1811 in patients (pts) with HER2-expressing advanced gynecological cancers (Gynecol C): A phase 2 study.

5612 Background: SHR-A1811 is a novel an antibody-drug conjugate consisting of a humanized HER2-directed monoclonal antibody, cleavable tetrapeptide-based linker, and DNA topoisomerase I inhibitor. We assessed SHR-A1811 in HER2-expressing advanced Gynecol C. Methods: Pts with ovarian cancer (OC) that had recurrence within 6 mo of last platinum-based therapy, and recurrent/metastatic endometrial cancer (EC) or cervical cancer (CC) that failed standard therapy were enrolled. Pts received SHR-A1811 at 4.8 or 6.4 mg/kg (Q3W, IV). The primary endpoint was ORR per RECIST v1.1. Results: As of Dec 25, 2024, 108 pts were enrolled (ECOG PS 1: 71.3%, prior VEGFR inhibitors: 53.7%, prior immunotherapies: 24.1%) including 46 pts with OC, 27 EC, and 35 CC. Rate of pts with HER2 IHC 3+ was 10.9%, 14.8%, and 31.4%; IHC 2+ was 54.3%, 70.4%, and 37.1%, respectively. The median follow-up was 8.1 mo (IQR, 4.7–10.7). For pts with OC, EC, and CC, ORR was 56.1%, 50.0%, and 63.6%, and PFS was 8.5 mo (95% CI, 5.7–NR), 5.6 mo (95% CI, 4.1–NR), and 10.7 mo (95% CI, 6.9–NR), respectively. In the 4.8 mg/kg cohort, for OC, EC, and CC, ORR was 56.8%, 52.0%, and 61.3%, and PFS was 8.5 mo (95% CI, 5.6–11.3), 7.2 mo (95% CI, 4.1–NR), and 10.7 mo (95% CI, 6.2–NR), respectively. Among OC, EC, and CC pts, ORR was 66.7% in 30 pts, 43.5% in 23 pts, and 66.7% in 24 pts with HER2 IHC 2+/3+, respectively. Additional antitumor activities are shown in Table. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 84 (77.8%) pts, with the most common being decreased neutrophil count (62.0%), decreased white blood cell count (48.1%), and anemia (28.7%). No TRAEs leading to discontinuation of treatment or deaths were reported. Conclusions: SHR-A1811 showed encouraging activity and manageable safety profile in pts with HER2-expressing advanced Gynecol C. Clinical trial information: NCT05896020 . Antitumor activity. 4.8 or 6.4mg/kg 4.8 mg/kg OC (N=46) EC (N=27) CC (N=35) Total (N=108) OC (N=42) EC (N=26) CC (N=33) Total (N=101) ORR a 23 (56.1) 13 (50.0) 21 (63.6) 57 (57.0) 21 (56.8) 13 (52.0) 19 (61.3) 53 (57.0) DCR a 36 (87.8) 24 (92.3) 31 (93.9) 91 (91.0) 33 (89.2) 23 (92.0) 29 (93.5) 85 (91.4) DOR, mo b 8.5(5.8–NR) 7.0(2.8–NR) 9.5(5.7–NR) 8.5(6.7–NR) 8.5(5.8–NR) 7.0(2.8–NR) 9.5(4.2–NR) 8.5(6.9–NR) TTR, median(range), mo b 2.7(1.1–4.4) 1.5(1.1–5.3) 1.4(1.2–5.4) 1.4(1.1–5.4) 2.7(1.1–4.4) 1.5(1.1–5.3) 1.4(1.2–5.4) 1.4(1.1–5.4) PFS, mo c 8.5(5.7–NR) 5.6(4.1–NR) 10.7(6.9–NR) 8.3(6.8–11.3) 8.5(5.6–11.3) 7.2(4.1–NR) 10.7(6.2–NR) 8.5(6.2–11.3) 6-mo OS rate, % (95% CI) c 89.5(74.5–95.9) 85.4(60.3–95.2) 93.6(76.8–98.4) 90.2(82.0–94.8) 91.2(75.1–97.1) 84.6(58.4–94.9) 93.2(75.4–98.3) 90.5(81.8–95.1) Data are n (%), median (95% CI), or otherwise indicated. a In pts with baseline and at least one post-baseline assessments; N was 41, 26, 33, 100, 37, 25, 31, and 93. b In pts with confirmed CR or PR; N was 23, 13, 21, 57, 21, 13, 19, and 53. <ja