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.
Resources from the same session
683TiP - A phase I study of PARP inhibitor (niraparib) plus HSP90 inhibitor (pimitespib) in solid tumors: The NiraPim (EPOC2102) study
Presenter: Hiromichi Nakajima
Session: Poster session 01
684TiP - A phase I, open-label, multicenter, dose escalation and expansion study of HM97662 (EZH1/2 dual inhibitor) as a single agent in patients with advanced or metastatic solid tumors
Presenter: Bhumsuk Keam
Session: Poster session 01
685TiP - A phase I, multicenter trial (“KinLET”) of [177Lu]Lu-edotreotide for treatment of somatostatin receptor positive solid tumors or lymphoma, in patients two to less than 18 years of age
Presenter: Maria Cristina Mata Fernandez
Session: Poster session 01
687TiP - A phase I, first in human study of TORL-4-500 in patients with advanced cancer
Presenter: Jonathan Goldman
Session: Poster session 01
688TiP - Phase I dose escalation trial to evaluate safety and preliminary efficacy of ACR246, an innovative 5T4- antibody drug conjugate (ADC), in patients (pts) with advanced solid tumors
Presenter: Xihui Hu
Session: Poster session 01
689TiP - A phase I/IIa trial of Aurora-A inhibitor (JAB-2485) in adult patients with advanced solid tumors
Presenter: Vaia Florou
Session: Poster session 01
690TiP - HERTHENA-PanTumor01: A global phase II trial of HER3-DXd in metastatic solid tumors
Presenter: Thomas Powles
Session: Poster session 01
691TiP - PYNNACLE phase II trial of rezatapopt (PC14586) in solid tumors with a TP53 Y220C mutation
Presenter: Alison Schram
Session: Poster session 01
722P - Long-term patient-reported outcomes (PROs) with atezolizumab (atezo) + bevacizumab (bev) and chemotherapy (CT) for metastatic, persistent or recurrent cervical cancer (R/M CC): BEATcc (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030) randomised phase III trial
Presenter: Laurence Gladieff
Session: Poster session 01