Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Participants will receive a loading dose-1 of IMAB362 on Cycle 1 Day 1 followed by a lower dose-2 in subsequent every 3 weeks.

Participants will receive a loading dose-3 of IMAB362 on Day 1 of each cycle (every 3 weeks).

Zolbetuximab will be administered as a 2-hour intravenous infusion.

Zolbetuximab

Medical Director

The purpose of this study is to assess the safety, tolerability and antitumor activity of IMAB362 in Japanese subjects with locally advanced or metastatic Gastric or GEJ adenocarcinoma whose tumors have Claudin (CLDN) 18.2 Expression. This study will also assess pharmacokinetics and immunogenicity of IMAB362.

This study consists of two parts (Part 1: Safety; and Part 2: Expansion). First, the subjects will be enrolled in Safety Part with IMAB362 dose-1/2 (Arm A). Then the safety and tolerability of Arm A will be evaluated at Tolerability Evaluation Meeting (TEM). If there are no safety and tolerability concerns, enrollment for the Safety Part with IMAB362 dose-3 (Arm B) and the Expansion Part with IMAB362 dose-1/2 will be opened. For each part, participants who continue to derive clinical benefit and do not have intolerable toxicity from study treatment will be allowed to remain on treatment until treatment discontinuation criterion is met.

A Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma

A Phase 1 Open-label Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Any of the IMAB362 related AEs specified as the DLTs will be assessed during the first 3 weeks.

An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) guidelines (Version 4.03).

Number of participants with potentially clinically significant laboratory values will be reported as AEs.

Number of participants with potentially clinically significant body weight change will be reported as AEs.

Number of participants with potentially clinically significant vital sign values will be reported as AEs.

ECGs will be recorded with the participant in the supine position, after the subject has been lying down for approximately 5 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.

Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.

ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

ORR is defined as the proportion of participants who have a best overall response of CR or PR per RECIST 1.1.

DCR is defined as the proportion of participants who have a best overall response of CR, PR or stable disease (SD) per RECIST 1.1.

PFS is defined as the time from the date of first dosing until the date of radiological or clinical progressive disease per RECIST 1.1 or death from any cause, whichever is earliest.

OS is defined as the time from the date of randomization until the date of death from any cause.

DOR is defined as the time from the date of the first response (CR or PR) per RECIST 1.1 to the date of radiological progression or death, whichever occurs earlier.

AUCinf will be derived from the PK serum samples collected.

AUCinf (%extrap) will be derived from the PK serum samples collected.

AUClast will be derived from the PK serum samples collected.

AUCtau will be derived from the PK serum samples collected.

Cmax will be derived from the PK serum samples collected.

Ctrough will be derived from the PK serum samples collected.

tmax will be derived from the PK serum samples collected.

t1/2 will be derived from the PK serum samples collected.

CL will be derived from the PK serum samples collected.

Vss will be derived from the PK serum samples collected.

Vz will be derived from the PK serum samples collected.

Rac(AUC) will be derived from the PK serum samples collected.

Rac(Cmax) will be derived from the PK serum samples collected.

An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs will be graded using the CTCAE guidelines (Version 4.03).

ECGs will be recorded with the participant in the supine position, after the subject has been lying down for approximately 5 minutes. There should be at least 2 minutes between ECG measurements in case a repeat is needed. Any clinically significant adverse changes on the ECG will be reported as AEs.

Immunogenicity of IMAB362 will be assessed by the frequency of ADA-positive participants.

Astellas Pharma Inc

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Anti-Infective Agents

Oxaliplatin

Capecitabine

Epirubicin

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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.

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.

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.

Epirubicin will be administered at a dose of 50 mg/m\^2 as a 15-minute intravenous infusion on day 1 of each cycle.

epirubicin

Oxaliplatin will be administered at a dose of 130 mg/m\^2 as a 2-hour intravenous infusion on day 1 of each cycle.

oxaliplatin

The daily dose of capecitabine will be 1250 mg/m\^2. Capecitabine tablets to be given once daily at a dose of 625 mg/m\^2 orally in the evening of day 1 of each cycle and twice daily at a dose of 625 mg/m\^2 orally on days 2 to 21 of each cycle; the morning dose of capecitabine on day 1 of each cycle to be omitted due to administration of zolbetuximab, epirubicin and oxaliplatin.

capecitabine

Two different formats of zolbetuximab, comprising different strengths, to be provided. Vials contained 22 mg or 105 mg of zolbetuximab. Prior to administration, zolbetuximab will be reconstituted with 1.1 mL (22 mg zolbetuximab vials) or 5.0 mL (105 mg zolbetuximab vials) water for injection, which will result in a concentration of 20 mg/mL zolbetuximab. The extractable volume per vial will be 1 mL (for 22 mg zolbetuximab vials) or 5 mL (for 105 mg zolbetuximab vials). The reconstituted solution will be further diluted with sodium chloride 0.9% to a final concentration of 2 mg/mL zolbetuximab. Zolbetuximab will be administered as an intravenous infusion over 2 to 3 hours.

zolbetuximab

Executive Director

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.

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

A Randomized Phase II Multicenter, Open-Label Study Evaluating the Efficacy and Safety of IMAB362 in Combination With the EOX (Epirubicin, Oxaliplatin, Capecitabine) Regimen as First-Line Treatment of Patients With CLDN18.2-Positive Advanced Adenocarcinomas of the Stomach, the Esophagus or the Gastroesophageal Junction

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 compounds 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. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

PFS is defined as the time from randomization to the first observation of disease progression (based on central reading) or death from any cause (as assessed by the independent reviewer). Participants without documented progression or death will be censored as of the last tumor evaluation determining lack of progression.

An AE is defined as any unintended or undesirable, noxious or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study medication. Treatment-emergent adverse event (TEAE) are those AEs that started or worsened after the first dose of study medication.

Clinical PFS (CPFS) is defined as the time from randomization to the first observation of disease progression, either confirmed by computed tomography (CT) scans or by clinical evaluation, or death from any cause (as assessed by the independent reviewer with clinical PD considered as an event). Participants without documented progression or death will be censored as of the last tumor evaluation determining lack of progression.

Overall survival rate at 12 months after therapy initiation is defined as a proportion of participants alive after 12 months from first dose of any study drug.

OS is defined as the time from randomization to death from any cause or last contact (if alive).

TTP is defined as the time from randomization to the first observation of disease progression (based on central reading as assessed by the investigator reviewer). Participants without documented progression will be censored as of the last tumor evaluation determining lack of progression.

ORR is defined as the fraction of participants with a complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (as assessed by the investigator reviewer). CR according to RECIST v1.1 is defined as the disappearance of all target lesions, any pathological lymph node must have reduction in short axis to \< 10 mm, disappearance of all non-target lesions and normalization of tumor marker level should occur as well as no simultaneous appearance of new lesions. PR according to RECIST v1.1 is defined as at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter and no simultaneous increase in the size of any lesion or the appearance of new lesions.

DCR is defined as the fraction of participants with CR or PR or stable disease (SD) according to RECIST v1.1 (as assessed by the investigator reviewer). SD according to RECIST v1.1 is defined as neither sufficient shrinkage to qualify for PR or CR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter recorded since treatment started, measurements must meet the SD criteria at least once after study entry at a minimum interval not less than 6 weeks, no simultaneous increase in the size of any lesion or the appearance of new lesions should occur, evaluable lesions must remain stable or regress for this category.

DOR will be determined as the time when criteria for CR or PR are first met until the first date that recurrent or progressive disease or death occurs (as assessed by the independent reviewer).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma	NCT03528629	Gastric Cancer Gastro-esophage...	Zolbetuximab	20 Years -	Astellas Pharma Inc
Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer	NCT01630083	CLDN18.2-positi... CLDN18.2-positi... CLDN18.2-positi...	epirubicin oxaliplatin capecitabine zolbetuximab	18 Years -	Astellas Pharma Inc
A Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma	NCT03528629	Gastric Cancer Gastro-esophage...	Zolbetuximab	20 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for asp8951

Every month we try and update this database with for asp8951 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for asp8951

Every month we try and update this database with for asp8951 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for asp8951 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.