ESMO Congress 2024 | OncologyPRO

Abstract 649P

Background

Nectin-4 is a cell adhesion molecule that serves as an attractive therapeutic target for ADCs, due to its high expression in a variety of solid tumors. SHR-A2102 is a novel ADC comprised of a fully humanized IgG1 mAb against nectin-4, a cleavable linker, and a topoisomerase I inhibitor payload. Here we present results of the dose escalation (D-ESC) and dose expansion (D-EXP) parts of a phase 1 study of SHR-A2102 for treating solid tumors.

Methods

Patients (pts) with nectin-4 positive, locally advanced unresectable or metastatic solid tumors, who had failed or were intolerant to standard therapies or had no standard treatment, were given SHR-A2102 intravenously Q3W. Primary objectives were to assess safety and tolerability.

Results

As of Apr 9, 2024, 38 pts were enrolled (median age: 61 yrs; ≥3 lines of prior therapies: 60.5%; prior ICI: 78.9%). During D-ESC, 17 pts received SHR-A2102 at 2 to 10 mg/kg. Only 1 pt in the 10 mg/kg group experienced a DLT (grade 4 decreased platelet count), and MTD was not yet reached. During D-EXP, additional 10 and 11 pts were given SHR-A2102 at 6 and 8 mg/kg, respectively. Overall, grade 3/4 TRAEs occurred in 42.1% (16/38) of pts, with the most common (≥10%) being decreased WBC count (21.1%), anemia (18.4%), decreased neutrophil count (15.8%), and decreased lymphocyte count (13.2%). No treatment-related deaths occurred. Among 30 pts evaluable for tumor response, ORR was 23.3% and DCR was 76.7% (Table). In 16 heavily pretreated NSCLC pts evaluable for tumor response, ORR was 31.3% (non-sq, 50.0%; sq, 12.5%) and DCR was 87.5% (non-sq, 75.0%; sq, 100.0%; Table). Table: 649P

Anti-tumor activity

	Non-sq NSCLC (N=8)	Sq NSCLC (N=8)	All NSCLC (N=16)	All tumor types (N=30)
Best overall response, n (%)
PR	4 (50.0)	1 (12.5)	5 (31.3)	7 (23.3)
SD	2 (25.0)	7 (87.5)	9 (56.3)	16 (53.3)
PD	2 (25.0)	0	2 (12.5)	7 (23.3)
ORR, % (95% CI)	50.0 (15.7–84.3)	12.5 (0.3–52.7)	31.3 (11.0–58.7)	23.3 (9.9–42.3)
DCR, % (95% CI)	75.0 (34.9–96.8)	100.0 (63.1–100.0)	87.5 (61.7–98.5)	76.7 (57.7–90.1)

Non-sq, non-squamous; sq, squamous.

Conclusions

SHR-A2102 showed a manageable safety profile and promising anti-tumor activity. Indication-specific cohorts are being recruited during the efficacy expansion part.

Clinical trial identification

NCT05701709; Release date: Jan 27, 2023.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

X. Li, Y. Huang, L. Song: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.