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

283

Events

198

Median

10.8 mo

Placebo + mFOLFOX6

282

Events

224

Median

8.4 mo

Number at Risk

Months	0	6	12	18	24	30	36
ZELVARA + mFOLFOX6	283	209	125	66	29	9	0
Placebo + mFOLFOX6	282	185	84	28	3	0	0

Overall Survival — BEACON-1

HR 0.74(95% CI: 0.60–0.92)p=0.0041

ZELVARA + mFOLFOX6

283

Events

168

Median

18.6 mo

Placebo + mFOLFOX6

282

Events

195

Median

15.2 mo

Number at Risk

Months	0	6	12	18	24	30	36
ZELVARA + mFOLFOX6	283	241	189	142	102	69	44
Placebo + mFOLFOX6	282	230	167	114	73	43	22

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

OS Subgroup Analysis — BEACON-1

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

ORR: 48.6%

Responder (≤-30%)

Stable Disease

Progressive (≥+20%)

Objective Response Rate — BEACON-1

Response	ZELVARA + mFOLFOX6	Placebo + 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%

Important Safety Information

INDICATIONS AND USAGE

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. CLDN18.2 positivity should be determined by an FDA-approved test.

Warnings and Precautions

Nausea and Vomiting: ZELVARA can cause severe nausea and vomiting. In the BEACON-1 trial, nausea occurred in 70.2% of patients treated with ZELVARA plus chemotherapy, including Grade 3 events in 14.8%. Vomiting occurred in 64.8%, including Grade 3 events in 12.1%. Administer antiemetic prophylaxis prior to and during treatment. Withhold, dose reduce, or permanently discontinue based on severity. Infusion-Related Reactions: Infusion-related reactions have been reported. Monitor patients during and after infusion. Interrupt or slow the rate of infusion for mild to moderate reactions. Permanently discontinue for severe or life-threatening reactions. Embryofetal Toxicity: Based on its mechanism of action and findings from animal studies, ZELVARA can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.

Adverse Reactions

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%). Serious adverse reactions occurred in 42% of patients treated with ZELVARA plus chemotherapy, including vomiting (8.2%), nausea (4.1%), dehydration (3.8%), and decreased appetite (2.4%). Fatal adverse reactions occurred in 2.1% of patients.

Drug Interactions

No formal drug interaction studies have been conducted with ZELVARA. No clinically significant pharmacokinetic interactions are expected based on the known elimination pathways of celdatuzumab.

Use in Specific Populations

Pregnancy: ZELVARA can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Lactation: Advise women not to breastfeed during treatment and for 3 months after the last dose. Females and Males of Reproductive Potential: Verify pregnancy status prior to initiation. Advise females to use effective contraception during treatment and for 3 months after the last dose. Pediatric Use: The safety and efficacy of ZELVARA have not been established in pediatric patients. Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. ZELVARA has not been studied in patients with moderate or severe hepatic impairment.

Efficacy Data

Progression-Free Survival — BEACON-1

Number at Risk

Overall Survival — BEACON-1

Number at Risk

PFS Subgroup Analysis — BEACON-1

OS Subgroup Analysis — BEACON-1

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

Objective Response Rate — BEACON-1

WARNING: NAUSEA AND VOMITING

Important Safety Information

INDICATIONS AND USAGE

Warnings and Precautions

Adverse Reactions

Drug Interactions

Use in Specific Populations