720MO - IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with advanced gynecological cancers (Gynecol C): Results from a phase I study

Background

IBI354 is an ADC consisting of trastuzumab (anti-HER2 antibody) conjugated to a topoisomerase I inhibitor. We report safety and efficacy of IBI354 in pts with advanced Gynecol C in a phase 1 study.

Methods

Eligible pts with HER2 IHC 1+, 2+ or 3+ advanced cervical cancer (CC), endometrial cancer (EC), or platinum-resistant ovarian cancer (OC) who failed or were intolerant to standard treatment were enrolled from China and Australia. Pts received IBI354 at 6, 9, or 12 mg/kg Q3W. Primary endpoint was safety. Secondary endpoints were ORR, DCR, DoR, and PFS per RECIST v1.1.

Results

As of Mar 22, 2024, 129 pts were enrolled (median age: 57.0 yrs, ECOG PS 1: 69.8%, prior treatment regimens ≥2: 82.2%) including 89 pts with OC, 26 CC, and 14 EC. HER2 alterations in most pts were IHC 1+ (65.6%) and 2+ (27.3%); 7.0% were IHC 3+. Median treatment duration was 12.3 weeks (range: 3.1-33.3). Treatment-related adverse events (TRAEs) occurred in 105 (81.4%) pts and grade ≥3 TRAEs in 21 (16.3%) pts. Most common TRAEs (≥ 20%) were anemia (34.1%), leukopenia (30.2%), nausea (29.5%), and neutropenia (21.7%). Interstitial lung disease was not observed. Serious TRAEs occurred in 7.0% pts. No TRAEs led to treatment discontinuation or death. TRAE led to dose reduction in 1 (0.8%) pt. The safety profile of IBI354 in Gynecol C was comparable with the whole study cohort. As of Apr 25, 2024, for pts with at least one tumor assessment (n = 124), ORR was 39.5% (95%CI: 30.9-48.7) and DCR was 83.1% (95% CI:75.3-89.2). In pts with OC (n = 86), ORR was 41.9% (95% CI: 31.3-53.0) and DCR was 81.4% (95% CI: 71.6-89.0). For the 40 OC pts at 12 mg/kg cohort, ORR and DCR were 45.0% (95% CI: 29.3-61.5) and 90.0% (95% CI: 76.3-97.2), respectively. For the 14 pts with HER2^2/3+ CC and EC, ORR and DCR was 57.1% (95% CI: 28.9-82.3) and 92.9% (95% CI: 66.1-99.8) including 1 pt (EC) achieved complete response and 7 pts (4 CC and 3 EC) achieved partial response. DoR and PFS were immature.

Conclusions

IBI354 was well tolerated and showed promising efficacy in pts with advanced Gynecol C. Clinical development of IBI354 in these tumors is ongoing. More data will be updated at the meeting.

Clinical trial identification

NCT05636215.

Editorial acknowledgement

Legal entity responsible for the study

Innovent Biologics (Suzhou) Co., Ltd.

Funding

Innovent Biologics (Suzhou) Co., Ltd.

Disclosure

H. Zhou: Financial Interests, Personal and Institutional, Full or part-time Employment: Innovent Biologics (Suzhou) Co., Ltd. All other authors have declared no conflicts of interest.