advanced adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction MedDRA version: 20.0 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10001173
Conditions
Interventions
Product Name: IMAB362
Product Code: IMAB362
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: IMAB362
Sponsors
Astellas Pharma Global Development Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction (2) Inoperable locally advanced disease or resections with R2 outcome or recurrent or metastatic disease. After receiving treatment cycles 2 and 4 of this study protocol, patients will be reevaluated for resectability according to the institutional guidelines. (3) CLDN18.2 expression confirmed by immunohistochemistry on paraffin embedded tumor tissue sample. Tumors with a staining intensity of 2+ or 3+ (the sum is decisive) in at least 40 % of the tumor cells. (4) Measurable and/or non-measurable disease as defined according to RECISTv1.1. (5) Age = 18 years. (6) Written Informed Consent Form. (7) ECOG performance status (PS) 0-1. (8) Life expectancy > 3 months. (9) HER2/neu negative patients and patients with HER2/neu positive status but not eligible to trastuzumab therapy in discretion of the investigator. (10) Adequate cardiac function. Formal measurement of left cardiac ejection fraction is = 55%. (11) Adequate hepatic function; bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: (1) Prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies. (2) Prior severe allergic reaction or intolerance to the chemotherapeutics used in this study or any excipient in the respective formulations. (3) Previous chemotherapy for advanced disease. (4) Previous perioperative chemotherapy with curative intention within 6 months (counted from the stop date of the perioperative chemotherapy), of start of study treatment. If interval is longer than 6 months, patients are allowed. (5) Radiotherapy within 4 weeks of start of study treatment (cycle 1, day1; 2 week interval allowed if palliative RTx given to bone metastatic side peripherally and patient recovered from acute toxicity). (6) Other investigational agents or devices concurrently or within 4 weeks prior to this study (cycle 1, day 1). (7) Known HIV infection or known symptomatic hepatitis (A, B, C). (8) Symptomatic cerebral metastases. (9) Clinically significant (i.e. active) cardiac disease. History of myocardial infarction or hospitalization for congestive heart failure within 12 months of enrollment. (10) Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial including, but not limited to any of the following: ongoing or active infection requiring parenteral antibiotics, uncontrolled hypertension, present cardiac arrhythmia with serious hemodynamic consequences or unstable angina pectoris. (11) Psychiatric illness or social situations that would preclude study compliance. (12) Pregnancy or breastfeeding. (13) Gastric bleeding within last 2 weeks, only symptomatic peptic ulcer. (14) Concurrent systemic immunosuppressive therapy, in particular systemic corticoids should be stopped 2 weeks prior to therapy (Cycle 1, Day 1). Inhaled and topically applied steroids are the exception and allowed. Systemic steroids should be avoided as long as patient is under study medication. Exception is otherwise uncontrollable nausea/vomiting. (15) Previous treatments with maximum cumulative doses of epirubicin >500 mg/m² and/or other anthracyclines and anthracenediones. (16) Treatment with Sorivudine or analogs. (17) Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible). (18) Malabsorption syndrome or inability to take oral medication (administration of capecitabine by naso-gastric or jejunostomy feeding tube is permitted). (19) Known dihydropyrimidine dehydrogenase (DPD) deficiency. (20) History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan only if clinically relevant. (21) Patients should have no evidence of dyspnea at rest. (22) Prior or current active autoimmune disease (like inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis or other rheumatologic disease)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Progression-free survival (PFS) • Safety and tolerability of IMAB362 in combination with EOX ; Secondary Objective: • Survival rate at 12 months after initiation of therapy • Overall survival (OS) • Time to progression (TTP) • Objective tumor response (ORR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 • Disease control rate (DCR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 • Duration of response (DOR) ; Primary end point(s): PFS is defined as the time from randomization to the first observation of disease progression or death from any cause. Patients without documented progression or death will be censored as of the last Tumor evaluation determining lack of progression. Safety and tolerability of IMAB362 in combination with EOX. ; Timepoint(s) of evaluation of this end point: Imaging will be performed to determine tumor burden at the following timepoints: • Baseline: =9 - 1 days prior to initiation of therapy (baseline) if the last assessment is older than 4 weeks • 6-weekly intervals until week 31, meaning week 7, 13, 19, 25, 31 (day 1 ± 4 days of these weeks) • every 12 weeks thereafter, meaning week 40, 49, ff (day 1± 4 days of these weeks) • anytime in between if there is clinical indication for progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to Progression is defined as the time from randomization of therapy to the first observation of confirmed disease progression. For patients who have not progressed either clinically or on the last scan, they will be censured as of the last tumor evaluation. • To determine survival status at 12 months following initiation of therapy each patient will be classified as alive or dead (irrespective of cause of death). For this purpose, upon completion of the last cycle, all patients will continue to be followed until death or loss to follow up. Patients who discontinue treatment due to progression will be followed in the same manner. • Overall survival is defined as the time from randomization to death from any cause or last contact if alive. • Objective Response Rate comprises the fraction of patients with CR, PR according to RECIST v1.1. It is set in relation to the FAS set and PP population. • Disease Control Rate is defined as the fraction of patients with CR or PR or SD according to RECIST v1.1. It is set in relation to the FAS set and PP population. • Duration of response is determined as the time when criteria for CR, PR, SD are first met until the first date that recurrent or progressive disease or death occur. ; Timepoint(s) of evaluation of this end point: Timepoints for all imaging assessments and tumor marker level evaluation to determine CR, PR, SD or PD are: • Imaging will be performed to determine tumor burden at the following timepoints: • Baseline: =9 - 1 days prior to initiation of therapy (baseline) if the last assessment is older than 4 weeks • 6-weekly intervals until week 31, meaning week 7, 13, 19, 25, 31 (day 1 ± 4 days of these weeks) • every 12 weeks thereafter, meaning week 40, 49, ff (day 1± 4 days of these weeks) | — |
Countries
Bulgaria, Czech Republic, Germany, Latvia, Russian Federation, Ukraine
Contacts
Public ContactProject Manager
PSI CRO
Outcome results
None listed