The US Food and Drug Administration on Friday approved Astellas' Vyloy (zolbetuximab-clzb) with chemotherapy as a first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive.

In zolbetuximab vs PBO arms, median follow-up was 17.8 vs 15.1 mo for PFS and 26.1 vs 26.2 mo for OS, respectively. Median PFS in zolbetuximab vs PBO arms was 8.3 vs 6.8 mo (HR 0.68 [95% CI 0.55, 0.85], P = 0.0004). Median OS in zolbetuximab vs PBO arms was 14.3 vs 12.2 mo (HR 0.77 [95% CI 0.62, 0.95], P = 0.0079); 24-mo OS rate was 28.3% vs 18.8%, with follow-up ongoing through final analyses....Zolbetuximab + CAPOX continued to demonstrate statistically significant improvement in PFS and OS compared with PBO + CAPOX, with no new safety signals, supporting zolbetuximab + CAPOX as a potential new option for 1L treatment of patients with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma.

Median OS was 18.2 vs 15.6 mo (HR 0.78 [95% CI 0.64, 0.95], P = 0.0067), with follow-up ongoing until final analysis; 24-mo OS rate was 37.7% vs 29.1%....With longer follow-up, zolbetuximab + mFOLFOX6 continued to demonstrate statistically significant improvement in PFS and OS compared with PBO + mFOLFOX6, with no new safety signals—supporting zolbetuximab + mFOLFOX6 as a potential new option for 1L treatment of pts with CLDN18.2+, HER2–, LA unresectable or mG/GEJ adenocarcinoma.

GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118)...Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma.

Astellas Pharma Inc...announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the company’s Biologics License Application (BLA) for zolbetuximab, a first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive. If approved, zolbetuximab would be the first CLDN18.2-targeted therapy available in the U.S. for these patients...The BLA is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.

Targeting CLDN18.2 with zolbetuximab significantly prolonged progression-free survival and overall survival when combined with mFOLFOX6 versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Zolbetuximab plus mFOLFOX6 might represent a new first-line treatment in these patients.

507 pts were randomized 1:1 to zolbetuximab + CAPOX (N = 254) or PBO + CAPOX (N = 253). Both PFS (median 8.21 vs 6.80 mo, HR 0.687, P=0.0007) and OS (median 14.39 vs 12.16 mo, HR 0.771, P=0.0118) were significantly prolonged with zolbetuximab + CAPOX (Table); in pts with measurable disease, ORR (95% CI) was 53.8% (46.58−60.99) vs 48.8% (41.76−55.84) in zolbetuximab vs PBO arm...Targeting CLDN18.2 with zolbetuximab combined with CAPOX significantly prolonged PFS and OS in 1L pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma.

PFS was statistically significantly improved with zolbetuximab + mFOLFOX6 (median 10.61 vs 8.67 mo, HR 0.751, P=0.0066; Table). OS was also significantly improved (median 18.23 vs 15.54 mo, HR 0.750, P=0.0053, < 0.0135 as boundary; Table)...Targeting CLDN18.2 with 1L zolbetuximab combined with mFOLFOX6 statistically significantly prolonged PFS and OS in pts with CLDN18.2+/ HER2−, LA unresectable or mG/GEJ adenocarcinoma.