Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer (FAST)

Astellas

Status and phase: Completed; Phase 2

Conditions: CLDN18.2-positive Gastric Adenocarcinoma; CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction; CLDN18.2-positive Adenocarcinoma of Esophagus

Treatments: Drug: oxaliplatin; Drug: capecitabine; Drug: epirubicin; Drug: zolbetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01630083

8951-CL-0202 (Other Identifier)

2011-005285-38 (EudraCT Number)

GM-IMAB-001-03

Details and patient eligibility

About

The purpose of the trial is to assess the therapeutic effects and the safety profile of IMAB362 combined with EOX (epirubicin, oxaliplatin, capecitabine) as first-line treatment for patients with advanced adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction compared to EOX alone.

Furthermore, sufficient binding of IMAB362 to the target cells is necessary for antitumoral activity. Thus, two dose levels ensuring a serum level above the in vitro predicted clinical efficacy threshold will be investigated.

Enrollment: 252 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction
• Inoperable locally advanced disease or resections with R2 outcome or recurrent or metastatic disease.
• CLDN18.2 expression confirmed by immunohistochemistry in paraffin embedded tumor tissue sample.
• Measurable and/or non-measurable disease as defined according to RECISTv1.1
• Age ≥ 18 years
• Written Informed Consent Form
• ECOG performance status (PS) 0-1
• Life expectancy > 3 months
• HER2/neu negative patients and patients with HER2/neu positive status but not eligible to trastuzumab therapy in discretion of the investigator.
• Adequate cardiac, hepatic, renal, hematologic function.

Exclusion criteria

• Prior severe allergic reaction or intolerance to a monoclonal antibody, to the chemotherapeutics used in this study or any excipient in the respective formulations.
• Previous chemotherapy for advanced disease.
• Previous perioperative chemotherapy with curative intention within 6 months of start of study treatment. If interval is longer than 6 months (counted from the stop date of the perioperative chemotherapy), patients are allowed.
• Known HIV infection or known symptomatic hepatitis (A, B, C).
• Symptomatic cerebral metastases.
• Pregnancy or breastfeeding.
• Previous treatments with maximum cumulative doses of epirubicin > 500 mg/m² and/or other anthracyclines and anthracenediones.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.

Trial design

252 participants in 3 patient groups

EOX Treatment

Active Comparator group

Description:

Participants will receive up to 8 cycles of epirubicin, oxaliplatin and capecitabine (EOX) chemotherapy treatment alone (50 mg/m\^2 epirubicin intravenously on day 1 of each cycle, 130 mg/m\^2 oxaliplatin intravenously on day 1 of each cycle, 625 mg/m\^2 capecitabine orally twice daily on days 1 to 21 of each cycle). The first dose of capecitabine to be taken in the evening of day 1.

Treatment:

Drug: epirubicin

Drug: capecitabine

Drug: oxaliplatin

EOX+zolbetuximab 800/600 mg/m^2

Experimental group

Description:

Participants will received up to 8 cycles of EOX chemotherapy treatment in combination with zolbetuximab administered as loading dose of 800 mg/m\^2 intravenously on day 1 of cycle 1 followed by 600 mg/m\^2 intravenously on day 1 of each subsequent cycle. Zolbetuximab to be administered prior to EOX chemotherapy. After completion of the EOX treatment phase, participants will be permitted to continue zolbetuximab monotherapy (600 mg/m\^2 every 3 weeks to be administered intravenously as a 2-hour infusion) until progressive disease (PD), withdrawal of consent or unacceptable toxicity. PD per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5mm must also be demonstrated, unequivocal progression of existing non-target lesions and appearance of one or more new lesions is considered progression.

Treatment:

Drug: zolbetuximab

Drug: epirubicin

Drug: capecitabine

Drug: oxaliplatin

EOX+zolbetuximab 1000 mg/m^2

Experimental group

Description:

Participants will receive up to 8 cycles of EOX chemotherapy treatment in combination with zolbetuximab 1000 mg/m\^2 intravenously on day 1 of each cycle. Zolbetuximab to be administered prior to EOX chemotherapy. After completion of the EOX treatment phase, participants will be permitted to continue zolbetuximab monotherapy (1000 mg/m\^2 every 3 weeks administered intravenously as a 2-hour infusion ) until PD, withdrawal of consent or unacceptable toxicity.

Treatment:

Drug: zolbetuximab

Drug: epirubicin

Drug: capecitabine

Drug: oxaliplatin