Zolbetuximab Combo Boosts Survival in Select Gastric Cancer Population

Patients with HER2-negative, CLDN18.2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials experienced improved survival with zolbetuximab (Vyloy) and chemotherapy when censoring data from those who discontinued treatment early due to nausea and vomiting, according to a news release from the developer, Astellas Pharma.¹ Additionally, those who were treated with a 3-drug antiemetic regimen prior to receipt of the zolbetuximab combination experienced lower rates of discontinuation due to nausea and vomiting.

Specifically, data from the trials showed that patients who received the 3-drug antiemetic regimen experienced a higher likelihood of not experiencing vomiting or nausea at dose 1 of cycle 1 at 75.3% and 60.8%, respectively.

When censoring data from patients who experienced early discontinuation or inadequate treatment exposure due to nausea and/or vomiting, treatment with zolbetuximab and chemotherapy exhibited significantly prolonged median progression-free survival (PFS) and overall survival (OS) outcomes compared with placebo and chemotherapy. The median PFS in the zolbetuximab and placebo arms were 10.4 months and 8.2 months, respectively, for an HR of 0.65. In the respective arms, the median OS was 17.9 vs 13.7 months, with an HR of 0.69.

Moreover, the analysis found that patients who received steroids experienced less frequent nausea or vomiting than those who did not. A total of 57.9% of patients who received steroids did not experience nausea vs 49.7% without steroids. Additionally, vomiting did not occur in 63.7% vs 62.6% of the respective groups. An association between faster infusion rates and early nausea and vomiting symptoms was observed, with investigators noting that symptoms may be mitigated with infusion-rate modifications.

“Early cycles are a critical window for supporting patients starting treatment for advanced gastric or GEJ cancer,” Timothy Forrest, RN, BSN, of Massachusetts General Hospital, explained in the news release.¹ “Since we know nausea and vomiting are common in this setting, preparing patients, monitoring closely, and using guideline-aligned supportive care can make a meaningful difference to their comfort and ability to continue treatment as planned.”

SPOTLIGHT Trial

The phase 3 SPOTLIGHT trial enrolled patients with CLDN18.2-positive advanced unresectable or metastatic gastric or GEJ adenocarcinoma and randomly assigned them 1:1 to receive oxaliplatin, leucovorin (folinic acid), and fluorouracil (mFOLFOX) plus zolbetuximab or placebo.²

Zolbetuximab was given as an intravenous infusion at a loading dose of 800 mg/m² on cycle 1, day 1 followed by 600 mg/m² every 3 weeks until study discontinuation criteria were met. Placebo was matched at the same schedule as the zolbetuximab.

The primary end point of the trial was PFS. Secondary end points included OS, time to confirmed deterioration (TTCD), objective response rate (ORR), duration of response (DOR), safety, and health-related quality of life (HRQOL).

GLOW Trial

A similar gastric or GEJ adenocarcinoma population was treated in the GLOW trial, with the key distinction being a difference in chemotherapy regimen used: patients in the GLOW trial received capecitabine and oxaliplatin (CAPOX) as opposed to mFOLFOX.³ A similar schedule was followed in the experimental and placebo arms between the trials. The primary end point was also PFS, with secondary end points also including OS, TTCD, ORR, DOR, safety, and HRQOL.

In both trials, the incidence of serious treatment-emergent adverse effects (TEAEs) was similar between both arms. The most common TEAEs of any grade reported with the zolbetuximab regimen included nausea, vomiting, and decreased appetite.

References

1. VYLOY™ (zolbetuximab) plus chemotherapy associated with enhanced survival outcomes when nausea and vomiting are effectively managed, according to new ad hoc analyses. News release. Astellas Pharma. January 8, 2026. Accessed January 8, 2026.
2. A study to compare zolbetuximab (IMAB362) and chemotherapy with placebo and chemotherapy in adults with gastric cancer. (Spotlight). ClinicalTrials.gov. Updated November 3, 2025. Accessed January 8, 2026. https://tinyurl.com/mst6aprm
3. A study of zolbetuximab (IMAB362) plus CAPOX compared with placebo plus CAPOX as first-line treatment of subjects with Claudin (CLDN) 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (GLOW). (GLOW). ClinicalTrials.gov. Updated October 27, 2025. Accessed January 8, 2026. https://tinyurl.com/4r47jk6v