JSKN003, a biparatopic anti-HER2 antibody drug conjugate (ADC), in the treatment of platinum-resistant ovarian cancer (PROC): Updated findings from two clinical trials.

5557 Background: JSKN003 is a biparatopic HER2-targeting ADC conjugated to a topoisomerase Ⅰ inhibitor with an average DAR of 4, who has preliminarily exhibited promising efficacy and safety in the treatment of PROC (QX Rao, et al. 2024 ESMO). This update presents the latest findings in patients (pts) who were not primary platinum-refractory. Methods: A pooled analysis of pts with PROC was performed from the phase Ⅰ JSKN003-101 trial conducted in Australia (NCT05494918) and phase Ⅰ/Ⅱ JSKN003-102 trial conducted in China (NCT05744427), which enrolled pts with advanced solid tumors to receive JSKN003 monotherapy. Tumor tissue samples were collected for central lab assessment of HER2-expression. Results: As of November 29, 2024, the median follow up time was 6.9 months. A total of 46 PROC pts received JSKN003 Q3W, with 2, 2, 40, 1 and 1 pts in 4.2, 5.2, 6.3, 7.3 and 8.4 mg/kg dose groups, respectively. Median age was 59.0 years, 65.2% had ≥ 3 prior lines of systemic therapy, 80.4% and 63.0% had previously received bevacizumab and PARP inhibitor, 39.1% were classified as HER2-expressing (IHC: 1+/2+/3+), with 21.7%, 10.9% and 6.5% in 1+, 2+ and 3+, respectively; 45.7% as HER2-no-expressing (IHC: 0), and 15.2% had no tissue samples for assessment. For 45 efficacy-evaluable pts, the overall response rate (ORR) was 64.4%, the median progression-free survival (PFS) was 7.1 months, and the 9-month overall survival (OS) rate was 84.9% (Table). JSKN003 demonstrated effectiveness across various HER2 expression subgroups. Notably, for pts with HER2-expression, the ORR reached 72.2%, with a median PFS of 9.4 months. Grade 3/4 treatment-related adverse events (TRAEs) occurred in only 6 (13.0%) pts. Serious TRAE occurred in only 4 (8.7%) pts. No TRAEs led to treatment discontinuation or death. The most common TRAE was Grade 1/2 Nausea (39.1%). Additionally, Grade 1/2 Interstitial lung disease (ILD) was observed in 4 (8.7%) pts, with no cases of Grade 3/4 reported. Conclusions: The maturer updated efficacy data reveal that JSKN003 provided substantial improvement in ORR, as well as benefit in PFS and OS in heavily treated PROC, irrespective of HER2 expression. The well tolerated toxicity with long-term observation was consistent with prior experience. A confirmatory trial (NCT06751485) is ongoing in all comers at any HER2 expression level to further support JSKN003 as a treatment option in this population. Clinical trial information: NCT05494918 and NCT05744427 . Efficacy summary. HER2 IHC Total(n = 45) 1+/2+/3+(n = 18) 0(n = 20) Unknown(n = 7) ORR, % (95% CI) 72.2 (46.5, 90.3) 55.0 (31.5, 76.9) 71.4 (29.0, 96.3) 64.4 (48.8, 78.1) CR, n (%) 2 (11.1) 0 0 2 (4.4) PR, n (%) 11 (61.1) 11 (55.0) 5 (71.4) 27 (60.0) Median PFS, month (95% CI) 9.4 (5.7, NE) 5.6 (4.1, NE) 9.6 (2.6, NE) 7.1 (5.6, 9.7) 9-mo OS Rate, % (95% CI) 83.0 (45.7, 95.6) 100.0 (100.0, 100.0) 85.7 (33.4, 97.9) 84.9 (56.6, 95.4)