ZELVARA
Full PI

Indication: ZELVARA® (celdatuzumab-mkrz) is indicated, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative, claudin 18.2 (CLDN18.2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Efficacy Data

ZELVARA demonstrated statistically significant improvements in overall survival (OS) and progression-free survival (PFS) across two pivotal Phase 3 trials in patients with CLDN18.2-positive, HER2-negative advanced gastric or GEJ adenocarcinoma.

BEACON-1: Randomized, double-blind, placebo-controlled. N=565. ZELVARA + mFOLFOX6 vs Placebo + mFOLFOX6. Primary endpoint: PFS per BICR. Median follow-up: 18.5 months.

Progression-Free Survival — BEACON-1

HR 0.73(95% CI: 0.59–0.91)p=0.0049
ZELVARA + mFOLFOX6
N
283
Events
198
Median
10.8 mo
Placebo + mFOLFOX6
N
282
Events
224
Median
8.4 mo

Number at Risk

Months061218243036
ZELVARA + mFOLFOX6283209125662990
Placebo + mFOLFOX62821858428300

Overall Survival — BEACON-1

HR 0.74(95% CI: 0.60–0.92)p=0.0041
ZELVARA + mFOLFOX6
N
283
Events
168
Median
18.6 mo
Placebo + mFOLFOX6
N
282
Events
195
Median
15.2 mo

Number at Risk

Months061218243036
ZELVARA + mFOLFOX62832411891421026944
Placebo + mFOLFOX6282230167114734322

Important Safety Information: The most common adverse reactions (≥20%) in patients receiving ZELVARA plus chemotherapy were nausea (70.2%), vomiting (64.8%), decreased appetite (42.1%), fatigue (38.4%), diarrhea (28.7%), and peripheral neuropathy (22.5%). See Full PI.

PFS Subgroup Analysis — BEACON-1

SubgroupNHR (95% CI)Favors ZELVARAFavors Control0.40.60.81.01.21.4All patients5650.73 (0.59–0.91)Age <653420.71 (0.54–0.93)Age ≥652230.76 (0.55–1.05)Male3780.70 (0.54–0.90)Female1870.79 (0.56–1.12)ECOG PS 02480.68 (0.50–0.93)ECOG PS 13170.77 (0.59–1.01)Gastric primary4120.72 (0.56–0.92)GEJ primary1530.76 (0.52–1.12)CLDN18.2 high (≥75%)3180.65 (0.49–0.86)CLDN18.2 moderate (≥40%)2470.84 (0.62–1.14)Asia2950.69 (0.52–0.92)Non-Asia2700.78 (0.58–1.05)Liver metastases: Yes1980.75 (0.54–1.04)Liver metastases: No3670.72 (0.55–0.94)Peritoneal metastases: Yes1680.78 (0.55–1.11)Peritoneal metastases: No3970.71 (0.55–0.91)

OS Subgroup Analysis — BEACON-1

SubgroupNHR (95% CI)Favors ZELVARAFavors Control0.40.60.81.01.21.4All patients5650.74 (0.60–0.92)Age <653420.72 (0.55–0.95)Age ≥652230.78 (0.56–1.08)Male3780.71 (0.55–0.92)Female1870.80 (0.57–1.13)ECOG PS 02480.70 (0.51–0.96)ECOG PS 13170.78 (0.60–1.02)Gastric primary4120.73 (0.57–0.93)GEJ primary1530.78 (0.53–1.14)CLDN18.2 high (≥75%)3180.67 (0.51–0.88)CLDN18.2 moderate (≥40%)2470.85 (0.63–1.15)Asia2950.71 (0.53–0.94)Non-Asia2700.79 (0.59–1.06)

Best Change from Baseline — BEACON-1 (Treatment Arm)

ORR: 48.6%
Responder (≤-30%)
Stable Disease
Progressive (≥+20%)

Objective Response Rate — BEACON-1

ResponseZELVARA + mFOLFOX6Placebo + mFOLFOX6
ORR (CR + PR)48.6%39.2%
Complete Response (CR)4.2%2.1%
Partial Response (PR)44.4%37.1%
Stable Disease (SD)32.8%36.5%
Progressive Disease (PD)14.1%19.8%