345MO - IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with advanced solid tumors and breast cancer (BC): Results from a phase I study

Background

IBI354 is an ADC comprising trastuzumab (anti-HER2 antibody) conjugated to a topoisomerase I inhibitor. We report a global multicenter, phase I study of IBI354 in pts with advanced solid tumors.

Methods

Eligible pts who failed or were intolerant of standard treatment were enrolled. HER2 alterations were assessed by IHC (1+/2+/3+), FISH, or NGS. IBI354 was administered at 0.8-15 mg/kg Q3W or Q2W. Dose levels ≥ 6 mg/kg were selected for dose expansion. Primary endpoint was safety. Secondary endpoints were ORR, DCR, DoR, and PFS per RECIST v1.1.

Results

As of Mar 22, 2024, 318 pts in China and Australia were enrolled (females: 89.9 %, median age: 56.0 yrs, ECOG PS 1: 73.0%, prior treatment regimens ≥2: 85.8%). Median treatment duration was 14.2 weeks (range: 3.1-37.3) with 215 (67.6%) pts still on treatment. No dose-limiting toxicity occurred across all dose levels explored. Treatment-related adverse events (TRAEs) occurred in 257 (80.8%) pts. Grade ≥3 TRAEs occurred in 16.7% of total pts (commonly [≥ 1%] being neutropenia [5.3%], leukopenia [3.5%], and anemia [2.5%]) and in 16.0% of pts in 12 mg/kg Q3W cohort. Serious TRAEs occurred in 11 (4.1%) pts. One (0.3%) pt required dose reduction and 1 (0.3%) required treatment discontinuation for TRAEs. No TRAE led to death. Interstitial lung disease (grade 1) occurred in 1 (0.3%) pt. As of Apr 25, 2024, for HER2-positive (HER2^{2+/FISH+ or 3+}) BC pts with at least one tumor assessment (n=44, median lines of prior treatments: 4), ORR was 61.4% (95% CI: 45.5-75.6) and DCR was 88.6% (95%CI: 75.4-96.2). ORR and DCR for each dose level were 57.1% (95% CI: 28.9-82.3) and 85.7% (95% CI: 57.2-98.2) for 6 mg/kg Q3W (n=14), 53.3% (95% CI: 26.6-78.7) and 86.7% (95% CI: 59.5-98.3) for 9 mg/kg Q3W (n=15), and 73.3% (95% CI: 44.9-92.2) and 93.3% (95% CI: 68.1-99.8) for 12 mg/kg Q3W (n=15). For the HER2-low (HER2^{1+ or 2+/FISH-}) BC pts with at least one tumor assessment at 12 mg/kg Q3W (n=26, median lines of prior treatments: 4), ORR was 53.8% (95% CI: 33.4-73.4) and DCR was 88.5% (95% CI: 69.8-97.6). DoR and PFS were immature.

Conclusions

IBI354 was well tolerated, including at higher doses up to 12 mg/kg. Promising efficacy was observed in both HER2-positive and HER2-low BC.

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, Inc. All other authors have declared no conflicts of interest.