Abstract 422P
Background
About 12–23% of patients with gastric/gastroesophageal junction (G/GEJ) cancer have HER2-positive disease. Although trastuzumab + chemotherapy prolonged median OS in these patients, the improvement remains unsatisfactory. At 2024 ASCO Gastrointestinal Cancers Symposium, we reported results of first-line treatment with HLX22 (novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + XELOX for patients with HER2-positive advanced G/GEJ cancer with a median follow-up duration of 14.3 months. Here we report the updated efficacy and safety with a median follow-up duration of 22.1 months.
Methods
This randomized, double-blind phase 2 trial enrolled patients with locally advanced or metastatic HER2-positive G/GEJ cancer and no prior systemic antitumor therapy. Patients were randomized 1:1:1 to receive HLX22 25 mg/kg + HLX02 + XELOX (group A), HLX22 15 mg/kg + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were IRRC-assessed PFS and ORR per RECIST v1.1.
Results
The study was unblinded 3 months after the last patient was enrolled. As of March 25, 2024, 53 patients were randomized to group A (n=18), B (n=17), and C (n=18). Updated efficacy results are shown in the table, with tumor assessments performed by IRRC. Serious treatment-related adverse events (TRAEs) were observed in 6 (33.3%) patients in group A, 1 (5.9%) in group B, and 1 (5.6%) in group C. 1 (5.6%) patient in group C died of a TRAE. Table: 422P
Updated efficacy and subsequent therapy
| Group A (n=18) | Group B (n=17) | Group C (n=18) | |
| mPFS, month (95% CI) | 13.7 (6.8, NE) | NR (9.9, NE) | 8.2 (5.4, 12.7) |
| HR ∗ (95% CI) | 0.4 (0.16, 1.03) | 0.1 (0.03, 0.43) | - |
| Confirmed ORR, % (95% CI) | 77.8 (52.4, 93.6) | 82.4 (56.6, 96.2) | 88.9 (65.3, 98.6) |
| ORR at week 36, % (95% CI) | 44.4 (21.5, 69.2) | 64.7 (38.3, 85.8) | 27.8 (9.7, 53.5) |
| ORR at week 75, % (95% CI) | 16.7 (3.6, 41.4) | 41.2 (18.4, 67.1) | 5.6 (0.1, 27.3) |
| mOS, month (95% CI) | 24.4 (14.4, NE) | NR (16.2, NE) | NR (6.4, NE) |
| HR ∗ (95% CI) | 0.7 (0.28, 1.87) | 0.5 (0.18, 1.48) | - |
| mDOR, month (95% CI) | 11.8 (5.5, NE) | NR (8.6, NE) | 6.8 (4.4, 11.3) |
| HR ∗ (95% CI) | 0.5 (0.19, 1.34) | 0.1 (0.02, 0.41) | - |
| Subsequent anti-HER2 therapy, n (%) | 3 (16.7) | 3 (17.6) | 8 (44.4) |
| ADC | 3 (16.7) | 3 (17.6) | 4 (22.2) |
| Antibody † | 0 | 1 (5.9) | 4 (22.2) ‡ |
∗Hazard ratio (HR) was estimated between group A and C, and between group B and C
†Includes bispecific antibody
‡1 patient in blinded trial. ADC, antibody-drug conjugate; m, median; NE, not evaluable; NR, not reached
Conclusions
The improved survival and antitumor response brought by the addition of HLX22 to HLX02 + XELOX as first-line therapy were maintained with manageable safety in HER2-positive G/GEJ cancer patients.
Clinical trial identification
NCT04908813; Released on 1 June 2021.
Editorial acknowledgement
Shiqi Zhong and Chen Hu of Shanghai Henlius Biotech, Inc.
Legal entity responsible for the study
Shanghai Henlius Biotech, Inc.
Funding
Shanghai Henlius Biotech, Inc.
Disclosure
F. Yang, H. Yu, J. Li, Q. Wang, J. Zhu: Financial Interests, Personal, Full or part-time Employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.