Abstract 675P
Background
JSKN003 is a novel HER2-directed antibody-drug conjugate (ADC) conjugated to a topoisomerase I inhibitor via a dibenzocyclooctyne tetrapeptide linker on the glycans of a humanized bispecific antibody. JSKN003-101 and JSKN003-102 is dose escalation and expansion studies in Australian and Chinese patients (pts) with metastatic solid tumors.
Methods
This is pooled analysis from pts enrolled in JSKN003-101 and JSKN003-102 with histologically documented HER2-positive (IHC 3+) solid tumors who failed prior systemic therapies, received JSKN003 monotherapy intravenously Q3W. The objectives were safety and efficacy of JSKN-003.
Results
As of 15th Mar 2024, 24 pts (7 CRC, 5 GC, 3 ESCA, 2 OC, 2 BTC, and 5 others) were enrolled and JSKN003 dosed across 6 dose levels, including 2.1 mg/kg, 4.2 mg/kg, 5.2 mg/kg, 6.3 mg/kg, 7.3 mg/kg and 8.4 mg/kg. 10 pts (41.7%) received ≥ 3 prior lines of therapy,6 pts(25%) received anti-HER2 ADC. The median duration of treatment was 13.9 (range,9.4,19.8) weeks, and 20 pts (83.3%) remained on treatment. Treatment-related adverse events (TRAEs) occurred in 23 pts (95.8%), and the mostly common grade 1 and 2 TRAEs were diarrhea (62.5%) and nausea (58.3%), infusion related reaction (29.2%), fatigue (25.0%).5 pts (20.8%) experienced grade ≥3 TRAEs, were neutropenia (8.3%), vomiting (4.2%), fatigue (4.2%) and abdominal discomfort (4.2%). 2 pts had interstitial lung disease, grade 2 (occurred in 6.3 mg/kg), both recovered thereafter. No TRAE led to death or discontinuation. 22 pts with tumor assessment, the ORR and DCR were 72.7% (95%CI: 49.8, 89.3) and 95.5% (95%CI: 77.2, 99.9). 5 pts who received prior anti-HER2 ADC, the ORR was 80% and median DOR was more than 30 weeks.
Conclusions
JSKN003 was well tolerated with encouraging preliminary antitumor activity in heavily pretreated pts with advanced HER2-positive (IHC ≥ 3+) solid tumors, which support further clinical development.
Clinical trial identification
NCT05494918; NCT05744427.
Editorial acknowledgement
Legal entity responsible for the study
Alphamab Oncology.
Funding
Alphamab Oncology.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
640P - Tumor response rate for hematologic and solid cancer drugs with FDA approval supported by single-arm trials
Presenter: Daniel Michaeli
Session: Poster session 01
641P - Phase I/II clinical and pharmacokinetic study of ecubectedin in combination with irinotecan in patients with selected advanced solid tumors
Presenter: Ana Gil Torralvo
Session: Poster session 01
642P - Phase I study of SHR-A2009, a HER3-targeted ADC, in pretreated EGFR-mutated NSCLC
Presenter: Qing Zhou
Session: Poster session 01
644P - Preliminary results of GQ1005 in metastatic HER2-low expressing breast cancer and HER2 positive gastric cancer
Presenter: Ting Deng
Session: Poster session 01
645P - Persistence and resistance of HER2 amplification after T-DM1 in a basket trial for patients with solid tumors
Presenter: Dazhi Liu
Session: Poster session 01
646P - A phase I trial of AVA6000, a fibroblast activation protein (FAP)-released, tumor microenvironment (TME)-targeted doxorubicin peptide drug conjugate in patients with FAP-positive solid tumors
Presenter: Christopher Twelves
Session: Poster session 01
Resources:
Abstract
647P - EphA2-targeting bicycle toxin conjugate (BTC) BT5528 in patients (pts) with advanced solid tumors: A phase I/II study
Presenter: Elisa Fontana
Session: Poster session 01
649P - Phase I study of SHR-A2102, a nectin-4 targeted ADC, in patients with advanced solid tumors
Presenter: Hua Zhong
Session: Poster session 01
650P - Initial results from a phase I/II study of BT7480, a novel nectin-4/CD137 bicycle tumor-targeted immune cell agonist, in patients (pts) with advanced solid tumors
Presenter: Kyriakos Papadopoulos
Session: Poster session 01