What question did this study set out to answer?

This research aims to evaluate the efficacy and safety of disitamab vedotin with toripalimab and chemotherapy in HER2-expressing gastric cancer.

June 5, 2026

Disitamab vedotin (DV) plus toripalimab (Tor) and chemotherapy (Chemo)/trastuzumab (Tra) for first-line (1L) HER2-expressing locally advanced or metastatic (la/m) gastric cancer (GC): Updated results from the RC48-C027 trial.

Key Points

This research aims to evaluate the efficacy and safety of disitamab vedotin with toripalimab and chemotherapy in HER2-expressing gastric cancer.
Randomized phase 2 trial including patients with HER2-high and HER2-intermediate/low gastric cancer.
Patients received DTC, DTT, or TTC for HER2-high and DTC or TC for HER2-intermediate/low cancer.
Primary endpoint was objective response rate and secondary endpoints included progression-free survival and overall survival.
For HER2-high, the objective response rate with DTT was 82.4% (95% CI 56.6-96.2).
DTCr demonstrated a median progression-free survival of 12.7 months (95% CI 2.4-NR) for HER2-intermediate/low patients.
Overall survival for HER2-high with DTT was 21.3 months, showing clinically meaningful trends with no new safety signals.

Abstract

LBA4026 Background: For patients (pts) with HER2-high (defined as IHC 3+, or IHC 2+/FISH+ based on Chinese CSCO GC guidelines) GC, current 1L therapy consisting of trastuzumab combined with pembrolizumab and chemotherapy offers limited efficacy. For pts with HER2-intermediate/low (defined as IHC 1+, or IHC 2+/FISH- as per Chinese guidelines) GC, no HER2-targeted precision treatment is available. Previous analysis of the RC48-C027 randomized phase 2 part showed notable objective response rates (ORRs): 82. 4% with DV + Tor + Tra in HER2-high GC; 72. 0% with DV + Tor + CAPOX (oxaliplatin and capecitabine) in HER2-intermediate/low GC, and lowering the CAPOX dose showed improved safety while maintaining efficacy (ORR: 71. 4%) (Shen et al. J Clin Oncol. 2025). We report updated results with extended follow-up, including tumor response, mature progression-free survival (PFS), and overall survival (OS) data. Methods: Pts with HER2-high, untreated, la/m gastric/gastroesophageal junction (G/GEJ) cancer were randomized at a ratio of 1: 1: 1 to receive DV + Tor + CAPOX (DTC), or DV + Tor +Tra (DTT), or Tor + Tra + CAPOX (TTC). For HER2-intermediate/low, untreated, la/m G/GEJ cancer, pts were randomized at 1: 1 to receive DV + Tor + CAPOX (DTC), or Tor + CAPOX (TC) in Stage 1; to enhance the overall tolerability, Stage 2 was initiated and randomized pts at 1: 1: 1 to receive DV + Tor + dose-reduced CAPOX (DTCr), or dose-reduced DV + Tor + dose-reduced CAPOX (DrTCr), or Tor + CAPOX (TC). The primary endpoint was ORR; secondary endpoints included PFS, duration of response (DoR), OS, and safety. Results: By the data cutoff (Jan 16, 2026), durable responses, a clinically meaningful improvement in PFS, and a favorable trend in OS were observed with DTT and DTCr. No new safety signals emerged. More outcomes are detailed in the Table. Conclusions: With extended follow-up, DTT and DTCr demonstrated sustained and clinically meaningful efficacy as 1L treatments for HER2-high and HER2-intermediate/low G/GEJ cancer, respectively. These findings warrant further confirmation in phase 3 trials. Clinical trial information: NCT05980481. HER2-high pts HER2-intermediate/low pts / Stage 1 Stage 2 DTC (n=18) DTT (n=17) TTC * (n=16) DTC (n=25) TC * (n=23) DTCr (n=14) DrTCr (n=15) TC * (n=16) OS follow-up (m), median 23. 3 21. 3 16. 6 Confirmed ORR ^, % (95% CI) 66. 7 (41. 0-86. 7) 82. 4 (56. 6-96. 2) 68. 8 (41. 3-89. 0) 75. 0 (53. 3-90. 2) 47. 8 (26. 8-69. 4) 76. 9 (46. 2-95. 0) 66. 7 (38. 4-88. 2) 60. 0 (32. 3-83. 7) DoR (m), median NR NR 13. 9 12. 4 10. 0 NR 12. 9 10. 6 PFS (m), median (95% CI) NR (8. 2-NR) 18. 0 (8. 5-NR) 13. 8 (3. 1-19. 6) 9. 9 (5. 8- NR) 7. 2 (5. 4-11. 3) 9. 5 (4. 8-NR) 12. 7 (2. 4-NR) 9. 9 (2. 8-13. 4) HR 0. 39 0. 58 / 0. 58 / 0. 59 0. 70 / OS (m), median</jat

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