Randomized Phase II trial Evaluating the Efficacy of ZolbEtuximab in the second-line for CLaudin18.2 Positive AdvanceD GAstric/EGJ Cancer Patients Previously Treated with Zolbetuximab and Platinum-Based Chemotherapy
ZELDA trial
MURO Kei
Aichi Cancer Center Hospital
1-1 Kanokoden, Chikusa-ku, Nagoya
+81-52-762-6111
kmuro@aichi-cc.jp
NARITA Yukiya
Kindai University Hospital
1-1 Kanokoden, Chikusa-ku, Nagoya
+81-52-762-611
yukiya.narita@aichi-cc.jp
Recruiting
June. 27, 2025
Sept. 03, 2025
216
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
a) Patients with histologically confirmed unresectable advanced or recurrent gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
b) Patients confirmed to be CLDN18.2-positive.(CLDN18 IHC demonstrating moderate to strong membranous staining in >= 75% of tumor cells)
c) Patients who are refractory to, or intolerant to agents other than zolbetuximab in, first-line combination therapy including a fluoropyrimidine, platinum-based agent, and zolbetuximab.It should be noted that, in the randomized phase 2 part, cases treated with ASP2138 will be allowed.
c-i) Patients who discontinued platinum agents for reasons other than disease progression during the combination therapy mentioned above, and experienced disease progression while continuing the remaining treatment.
Example: capecitabine + oxaliplatin + zolbetuximab followed by apecitabine + zolbetuximab
c-ii) Patients who changed either the fluoropyrimidine or platinum agent for reasons other than disease progression while continuing combination treatment, and subsequently experienced disease progression.
Example: 5-FU + oxaliplatin + zolbetuximab followed by capecitabine + oxaliplatin + zolbetuximab
d) Patients with at least one measurable or evaluable lesion per RECIST version 1.1.
e) Patients aged 18 years or older.
f) Patients with an ECOG Performance Status (PS) of 0 or 1.
g) Patients expected to have a survival of at least 3 months from the date of enrollment.
h) Patients with preserved major organ function confirmed within 14 days prior to enrollment, as defined below:
i. Absolute neutrophil count (ANC) >= 1,500 /mm^3
ii. Hemoglobin (Hb) >= 8.0 g/dL
iii. Platelets (Plt) >= 100,000 /mm^3
iv. Total bilirubin (T-Bil) <= 1.5 mg/dL
v. AST <= 120 U/L (<= 200 U/L in cases with liver metastases)
vi. ALT <= 120 U/L (<= 200 U/L in cases with liver metastases)
vii. Serum creatinine <= 1.5 mg/dL or creatinine clearance >= 30 mL/min (calculated using the Cockcroft-Gault formula or an equivalent method, and/or by 24-hour urine collection)
viii. Urine protein <= 1+
(If dipstick shows 2+ or more, eligibility is allowed if 24-hour urinary protein < 2 g or urinary protein-to-creatinine ratio (UPC) < 2.)
i) Cases confirmed to be HBs antigen negative (regardless of the timing of confirmation), patients must be receiving nucleos(t)ide analog therapy in accordance with hepatitis B management guidelines.
Consultation with a hepatology specialist is recommended in such cases.
j) Women of childbearing potential must agree to use highly effective contraception prior to the start of study treatment and throughout the study period. Male patients must be surgically sterile or agree to use highly effective contraception during the study and for 6 months after completion of treatment.
k) Patients who have voluntarily signed written informed consent after receiving a full explanation of the study prior to enrollment.
a) Patients with active multiple primary cancers (synchronous cancers or metachronous cancers with a disease-free interval of less than 3 years). However, patients with carcinoma in situ or mucosal carcinoma that is considered curatively treated by local therapy, non-metastatic prostate cancer not requiring systemic therapy, or other solid tumors that do not require treatment or are not expected to be adversely affected by the treatment protocol may be included if judged not to impact prognosis.
b) Patients with a history of treatment with angiogenesis inhibitors.
c) Patients with a history of taxane-based chemotherapy for incurable conditions.
*Patients who received taxanes as perioperative chemotherapy and have had at least 24 weeks since the last dose are not subject to this exclusion criterion.
d) Patients who are intolerant to zolbetuximab.
e) HER2-positive patients.
f) Patients with uncontrolled diabetes mellitus.
g) Patients with a history of deep vein thrombosis, pulmonary embolism, or other significant thromboembolic events (excluding catheter-related thrombosis or superficial vein thrombosis) within 3 months prior to enrollment.
h) Patients with significant (Grade 3-4) hemorrhagic disorders, vasculitis, or gastrointestinal bleeding within 3 months prior to enrollment.
i) Patients with a history of arterial thrombotic events such as myocardial infarction, unstable angina, cerebrovascular disorders, or transient ischemic attack within 6 months prior to enrollment.
j) Patients with a history of gastrointestinal perforation or fistula, or at high risk for perforation, within 6 months prior to enrollment.
k) Patients who have undergone major surgery (minor procedures such as lymph node biopsy, needle biopsy, or port placement are excluded), experienced serious wounds or unhealed injuries, peptic ulcers, or fractures within 4 weeks prior to enrollment.
l) Patients who have received blood transfusions within 2 weeks prior to enrollment.
m) Patients with symptomatic heart failure (NYHA Class II-IV) or symptomatic or uncontrolled arrhythmia.
n) Patients with uncontrolled hypertension not responsive to antihypertensive therapy (e.g., sustained systolic BP >160 mmHg or diastolic BP >100 mmHg for more than 4 weeks).
o) Patients receiving continuous systemic steroid therapy (oral or intravenous).
p) Patients with liver cirrhosis.
q) Patients with symptomatic brain metastases or leptomeningeal dissemination.
r) Patients with active infections.
s) Patients with pericardial, pleural, or ascitic effusions requiring frequent drainage or therapeutic intervention.
t) Patients with intolerance or a history of severe allergic or anaphylactic reactions to antibodies or human serum albumin.
u) Patients with evident interstitial lung disease on CT. However, radiation-induced fibrosis within the radiation field is acceptable.
v) Patients with psychiatric disorders or symptoms deemed to make participation in the trial difficult.
w) Female patients who are pregnant, may be pregnant, or are breastfeeding.
x) Any other patient deemed inappropriate for participation in the study by the investigator.
Group A (Control Arm): Nab-Paclitaxel + Ramucirumab Therapy
Day 1 of each cycle is defined as the day when either Nab-Paclitaxel or Ramucirumab is administered first, with one cycle consisting of 28 days. Administration continues unless criteria for protocol treatment discontinuation specified in "Section 7.5.2.1. Protocol Treatment Discontinuation Criteria" are met.
Group B (Experimental Arm): Nab-Paclitaxel + Ramucirumab + Zolbetuximab Therapy
After confirming safety in the Safety Lead-in Part, this treatment will be used as the experimental treatment in the Randomized Phase II Part.
Day 1 of each cycle is defined as the day when either Nab-Paclitaxel, Ramucirumab, or Zolbetuximab is administered first, with one cycle consisting of 28 days. Administration continues unless criteria for protocol treatment discontinuation specified in "Section 7.5.2.1. Protocol Treatment Discontinuation Criteria" are met.
Gastric Cancer, Gastroesophageal Cancer,
CLDN18.2, Zolbetuximab,
Safety lead-in part; Tolerability Evaluation
Randomized phase 2 part; Overall Survival in the Largest Analysis Population.
Overall Survival in All Registered Cases and Protocol-Eligible Cases
Progression-Free Survival (PFS)
Time to Treatment Success (TTS)
Time to Response (TTR)
Duration of Response (DoR)
Response Rate (RR)
Disease Control Rate (DCR)
Tumor Shrinkage Rate (TSR)
Early Tumor Shrinkage Rate (ETSR)
Incidence Rate of Adverse Events
Quality of Life (QOL) Evaluation
Astellas Pharma Inc.
Kyushu University Certified Institutional Review Board for Cli nical Trials
3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan, Fukuoka, Fukuo ka, Fukuoka
