A Study of Zolbetuximab Together with Pembrolizumab and Chemotherapy in Adults with Gastric Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

31 Jul 2025 → ongoing

Decision date (initial)

2025-07-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Astellas Pharma Global Development

External identifiers

EU CT number

2024-519773-19-00

ClinicalTrials.gov

NCT06901531

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of zolbetuximab plus pembrolizumab and chemotherapy (CAPOX or mFOLFOX6) compared with placebo plus pembrolizumab and chemotherapy (CAPOX or mFOLFOX6) (as first-line treatment)

Secondary objectives 5

1. To evaluate the activity and efficacy of zolbetuximab plus pembrolizumab and chemotherapy compared with placebo plus pembrolizumab and chemotherapy
2. To evaluate the efficacy of zolbetuximab plus pembrolizumab and chemotherapy compared with placebo plus pembrolizumab and chemotherapy
3. To assess the safety and tolerability of zolbetuximab in combination with pembrolizumab and chemotherapy
4. To evaluate the pharmacokinetics of zolbetuximab in combination with pembrolizumab and chemotherapy
5. To evaluate the immunogenicity profile of zolbetuximab in combination with pembrolizumab and chemotherapy

Conditions and MedDRA coding

Gastroesophageal Junction Adenocarcinoma

Study design 6 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002695-PIP01-19

Plan to share IPD

Yes

IPD plan description

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas’ data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant is ≥ 18 years of age at the time of signing informed consent.
2. Participant has histologically confirmed gastric or gastroesophageal adenocarcinoma
3. Participant has radiographically confirmed, locally advanced unresectable or metastatic disease within 28 days prior to randomization.
4. Participant has radiologically evaluable disease (measurable and/or nonmeasurable) according to RECIST V1.1, per investigator assessment, ≤ 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
5. Participant has Eastern Cooperataive Oncology Group performance status 0 to 1.
6. Participant has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
7. Participant must be a candidate to receive mFOLFOX6 or CAPOX and pembrolizumab.
8. Participant has a HER2-negative tumor.
9. Participant’s tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
10. Participant’s tumor expresses PD-L1 CPS ≥1 as determined by central IHC testing. Participants with known microsatellite instability-high or mismatch repair deficient status may enroll as long as they meet the PD-L1 positivity criteria set forth in this protocol.

Exclusion criteria 17

1. Participant has prior severe allergic reaction or intolerance to (zolbetuximab or other monoclonal antibodies, pembrolizumab, mFOLFOX6 or CAPOX).
2. Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.
3. Participant has significant gastric bleeding and/or untreated gastric ulcers that would preclude the participant from participation per investigator’s judgment.
4. Participant has unresolved pneumonitis or history of non-infectious pneumonitis such as immune-related pneumonitis, radiation induced pneumonitis.
5. Participant has history of central nervous system metastases and/or carcinomatous meningitis from gastric/gastroesophageal junction cancer.
6. Participant has a known history of a positive test for HIV infection or known active hepatitis B (positive HBsAg) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements.
7. Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
8. Participant has active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
9. Participant has a clinically significant disease or comorbidity that in the opinion of the investigator may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
10. Participant has another malignancy for which treatment is required, per investigator’s clinical judgment.
11. Participant has known dihydropyrimidine dehydrogenase deficiency (screening for dihydropyrimidine dehydrogenase deficiency should be conducted per local requirements). For EU-specific requirements, refer to section 10.9.1 of the protocol.
12. Participant has known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the participant ineligible).
13. Participant has sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving per investigator’s judgment.
14. Participant has significant cardiovascular disease, including any of the following: a. Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization. b. History of clinically significant ventricular arrhythmias (i.e., sustained; ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes). c. QTc interval > 450 msec for male participants; QTc interval > 470 msec for female participants. d. History or family history of congenital long QT syndrome. e. Cardiac arrhythmias requiring anti-arrhythmic medications (participants with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
15. Participant has ongoing or previous interstitial lung disease, active diverticulitis or peptic ulcerative disease, or solid organ or stem cell transplant or other uncontrolled or clinically significant medical disorders.
16. Participant has type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed
17. This criterion has been removed

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival, defined as the time from the date of randomization until the documented date of death from any cause

Secondary endpoints 6

1. Progression-free survival, defined as the time from the date of randomization until the date of radiologic disease progression (investigator-assessed per RECIST V1.1) or death from any cause, whichever is earlier
2. Objective response rate, defined as the proportion of participants who have a best overall response of complete response or partial response as investigator-assessed per RECIST V1.1
3. Duration of response, defined as the time from the date of the first response (complete response/partial response) until the date of disease progression as investigator-assessed per RECIST V1.1 or date of death from any cause, whichever is earlier
4. Safety and tolerability of zolbetuximab in combination with pembrolizumab and chemotherapy as evaluated by adverse events, electrocardiogram, vital signs, Eastern Cooperative Oncology Group performance status and safety laboratory assessments (NCI-CTCAE version 5.0)
5. Serum concentrations of zolbetuximab: end of infusion concentrations and concentration immediately prior to dosing at multiple dosing
6. Measurement of frequency of antidrug antibody-positive participants

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 13

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6145

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Third parties 13

Locations

11 EU/EEA countries · 126 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 551 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications