IBI354, an anti-HER2 antibody-drug conjugate, in patients with locally advanced unresectable or metastatic ovarian cancers: Updated results from a phase I trial.

5565 Background: IBI354 is an antibody-drug conjugate consisting of trastuzumab (anti-HER2 antibody) conjugated to a topoisomerase I inhibitor. It has showed manageable safety and encouraging efficacy in patients (pts) with advanced gynecologic cancers (including ovarian cancers [OC], Shu et al, abstract No. 720MO at 2024 ESMO annual meeting). Here, we present the updated safety and efficacy in OC. Methods: Eligible OC pts with HER2 alteration (IHC 1+, 2+, 3+ and/or ISH+ and/or NGS confirmed mutation or amplification) who failed or were intolerant to standard treatment were enrolled from China and Australia. Pts received IBI354 at 2−12 mg/kg every three weeks (Q3W) or Q2W. Primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and progression-free survival (PFS) per RECIST v1.1. Results: As of November 12, 2024, 92 pts were enrolled (median age, 58.0 years; Asian, 95.7%; White, 4.3%; ECOG PS 1, 73.9%; IHC 1+, 65.2%; IHC 2+, 29.3%). The median follow-up time was 11.0 months (range: 8.0−19.0). Median treatment duration was 24.1 (range: 3.1−60.3) weeks with 21 (22.8%) pts still on treatment. Treatment-related adverse events (TRAEs) occurred in 79 (85.9%) pts with grade ≥ 3 TRAEs in 27 (29.3%) pts. The most common TRAEs were anemia (51.1%), white blood cell count decreased (45.7%), neutrophil count decreased (40.2%), and nausea (35.9%). Serious TRAEs occurred in 10 (10.9%) pts. Interstitial lung disease or pneumonitis was observed in 1 (1.1%) pt, which was grade 2 and not related to IBI354 considered by the investigator. TRAEs led to dose reduction in 2 (2.2%) pts. No TRAEs led to treatment discontinuation or death. For efficacy-evaluable pts (who had at least 1 post-baseline tumor assessment) dosed at 12 mg/kg Q3W (n = 40), confirmed ORR and DCR reached 55.0% (95% CI: 38.5−70.7) and 90.0% (95% CI: 76.3−97.2), respectively. In 22 pts with confirmed response in 12 mg/kg Q3W dose group, the median DoR was not reached with events occurred in 6 (27.3%) pts, and 9-month DoR rate of 58.1% (24.2−81.2). The median PFS was 7.1 months (95% CI: 5.2−not reached) with events occurred in 21 (51.2%) pts. The median overall survival (OS) was not reached with events occurred in 12 (29.3%) pts, and the 9 month OS rate was 70.7% (95% CI: 54.3−82.2). For the pts with HER2 IHC 1+ OC dosed at 12 mg/kg Q3W (accounting for 67.5% [27/40] of efficacy-evaluable pts at 12 mg/kg Q3W), ORR and DCR reached 55.6% (95% CI: 35.3−74.5) and 88.9% (70.8−97.6), respectively. Conclusions: IBI354 was well tolerated with a manageable safety profile and showed promising efficacy in pts with locally advanced unresectable or metastatic OC, especially in pts with HER2 lower expression. Clinical trial information: NCT05636215 .