Novel ADC Checkpoint Inhibitor Combo Shows Promise in HER2+ GI Cancers
Arturo Loaiza-Bonilla, MD, MSEd, discusses the potential of disitamab vedotin, toripalimab, and chemotherapy/trastuzumab in first-line treatment.
Arturo Loaiza-Bonilla, MD, MSEd, systemwide chief of hematology and oncology at St. Lukes University Heath Network and co-founder and chief medical officer at Massive Bio, discusses the potential of disitamab vedotin (Aidixi), toripalimab (Loqtorzi), and trastuzumab (Herceptin) in first-line treatment.
A new triplet regimen combining disitamab vedotin, toripalimab, and chemotherapy is showing encouraging results in the first-line treatment of HER2-expressing gastric and gastroesophageal junction (GEJ) adenocarcinomas, according to findings presented in late-breaking abstract at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
The phase 2 segment of a phase 2/3 trial (NCT05980481) evaluated disitamab vedotin, an antibody-drug conjugate (ADC), combined with the PD-1 inhibitor toripalimab and chemotherapy in patients with locally advanced or metastatic HER2-expressing gastric or GEJ cancers. Patients were stratified by HER2 expression level to assess efficacy across a broader range of HER2-positive disease.
“The response rate with the triplet was about 82.4% compared with 68.8% in the control arm,” Loaiza-Bonilla says. The median progression-free survival had not yet been reached in the investigational arm, compared with 14.1 months in the control group, yielding a favorable hazard ratio of 0.59 (95% CI, 0.20-1.70).
Importantly, the benefit extended beyond HER2-overexpressing tumors. Patients with intermediate or low HER2 expression also saw improved outcomes, with a 72% response rate in the triplet group vs 47.8% in those receiving toripalimab plus chemotherapy alone. “This suggests that not all HER2-positive tumors behave the same—and that even low expressors may respond to targeted treatment,” he noted.
Adverse events were consistent with known profiles of ADC and checkpoint therapies, including diarrhea and cytopenias.
While the data remain early, Loaiza-Bonilla emphasizes the potential to expand treatment options for patients with HER2-expressing disease, especially those with limited expression who previously may not have qualified for HER2-targeted therapy.
“This is a novel ADC and PD-1 combination we haven’t tried before, and it may help us optimize care for a broader HER2-positive population.”
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