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A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of Zolbetuximab (IMAB362) in Participants With Claudin (CLDN) 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma

NCT03505320

Description:

The purpose of this study is to determine the Objective Response Rate (ORR) of zolbetuzimab as a single agent as assessed by an independent central reader. This study will also assess the ORR and Progression Free Survival (PFS) of zolbetuximab in combination with mFOLFOX6, assess the safety and tolerability, assess the effects on CLDN18.2 expression and assess the immunogenicity and immunomodulatory effects of zolbetuximab as a single agent and in combination with mFOLFOX6. This study will also evaluate the pharmacokinetics (PK) of zolbetuximab, oxaliplatin and fluorouracil (5-FU), evaluate health-Related Quality of Life (HRQoL), evaluate the Disease Control Rate (DCR), Duration of Response (DOR), PFS and Overall Survival (OS) of zolbetuximab as a single agent.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of IMAB362 in Participants With Claudin (CLDN) 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma
  • Official Title: A Phase 2 Study of IMAB362 as Monotherapy or in Combination With mFOLFOX6 in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma Whose Tumors Have High or Intermediate Claudin (CLDN) 18.2 Expression

Clinical Trial IDs

  • ORG STUDY ID: 8951-CL-0103
  • SECONDARY ID: 2017-002566-50
  • NCT ID: NCT03505320

Conditions

  • Pharmacokinetics of IMAB362
  • Gastric Cancer
  • Gastro-esophageal Junction (GEJ) Cancer
  • Pharmacokinetics of Oxaliplatin
  • Pharmacokinetics of Fluorouracil Bolus (5-FU)

Interventions

DrugSynonymsArms
IMAB362mFOLFOX6 plus IMAB362 (Cohort 2)
oxaliplatinmFOLFOX6 plus IMAB362 (Cohort 2)
leucovorinmFOLFOX6 plus IMAB362 (Cohort 2)
fluorouracilmFOLFOX6 plus IMAB362 (Cohort 2)

Purpose

The purpose of this study is to determine the Objective Response Rate (ORR) of IMAB362 as a single agent as assessed by an independent central reader. This study will also assess the ORR and Progression Free Survival (PFS) of IMAB362 in combination with mFOLFOX6, assess the safety and tolerability, assess the effects on CLDN18.2 expression and assess the immunogenicity and immunomodulatory effects of IMAB362 as a single agent and in combination with mFOLFOX6. This study will also evaluate the pharmacokinetics (PK) of IMAB362, oxaliplatin and fluorouracil (5-FU), evaluate health-Related Quality of Life (HRQoL), evaluate the Disease Control Rate (DCR), Duration of Response (DOR), PFS and Overall Survival (OS) of IMAB362 as a single agent.

Detailed Description

      This is a study to assess the antitumor activity of IMAB362, an Immunoglobulin (IgG1)
      chimeric monoclonal antibody directed against CLDN18.2, in subjects with recurrent locally
      advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors have
      high or intermediate CLDN18.2 expression. For each cohort, the study consists of the
      following periods: pre-screening; screening; treatment; and follow-up for disease
      progression. In addition, there will be a survival follow-up period for Cohort 1 subjects
      only.
    

Trial Arms

NameTypeDescriptionInterventions
IMAB362 (Cohort 1A and Cohort 1B)ExperimentalParticipants will be treated with IMAB362 on a 21-day cycle in which IMAB362 will be administered as a single agent every 3 weeks until disease progression, toxicity requiring cessation, start of another anti-cancer treatment or other treatment discontinuation criteria are met. Cohort 1B will be opened if at least 1 participant achieves a confirmed response (complete response [CR] or partial response [PR]) as assessed by an independent central reader.
  • IMAB362
mFOLFOX6 plus IMAB362 (Cohort 2)Active ComparatorParticipants will be treated with IMAB362 and mFOLFOX6 on a 42-day cycle in which IMAB362 is administered on days 1 and 22, and mFOLFOX6 is administered on days 1, 15 and 29; however, for the first cycle, IMAB362 will be administered on day 3 (instead of day 1) to allow for pharmacokinetic collection. Participants will receive 12 mFOLFOX6 treatments (4 cycles). Beginning at cycle 5, participants may continue on 5-FU and leucovorin along with IMAB362 for the remainder of the study per investigator's discretion. mFOLFOX6 treatment includes oxaliplatin: intravenous [IV] infusion, leucovorin: IV infusion, fluorouracil bolus: IV bolus, fluorouracil infusion: continuous IV infusion.
  • IMAB362
  • oxaliplatin
  • leucovorin
  • fluorouracil

Eligibility Criteria

        Inclusion Criteria:

          -  Female subject must either:

               -  Be of non-childbearing potential:

               -  Postmenopausal (defined as at least 1 year without any menses for which there is
                  no other obvious pathological or physiological cause) prior to screening, or

               -  Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy,
                  bilateral oophorectomy)

               -  Or, if of childbearing potential:

               -  Agree not to try to become pregnant during the study and for 6 months after the
                  final study drug administration

               -  And have a negative serum pregnancy test at screening (note: subjects with
                  elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated
                  non-pregnant status through additional testing are eligible)

               -  And, if heterosexually active, agree to consistently use 1 form of highly
                  effective birth control starting at screening and throughout the study period and
                  for 6 months after the final study drug administration

          -  Female subject must agree not to breastfeed starting at screening and throughout the
             study period, and for 6 months after the final study drug administration.

          -  Female subject must agree not to donate ova starting at screening and throughout the
             study period, and for 6 months after the final study drug administration.

          -  A sexually active male subject with a female partner(s) who is of childbearing
             potential is eligible if:

               -  Agree to use a male condom starting at screening and continue throughout study
                  treatment and for 6 months after the final study drug administration.

               -  If the male subject has not had a vasectomy or is not sterile as defined below
                  their female partner(s) is utilizing 1 form of highly effective birth control
                  starting at screening and continue throughout study treatment and for 6 months
                  after the male subject receives their final study drug administration.

          -  Male subject must agree not to donate sperm starting at screening and throughout the
             study period, and for 6 months after the final study drug administration.

          -  Male subject with a pregnant or breastfeeding partner(s) must agree to remain
             abstinent or use a condom for the duration of the pregnancy or time partner is
             breastfeeding throughout the study period and for 6 months after the final study drug
             administration.

          -  Subject has histologically confirmed gastric or GEJ adenocarcinoma.

          -  Subject has radiographically-confirmed, locally advanced, unresectable or metastatic
             disease within 28 days prior to the first dose of study treatment

          -  Subject has measurable disease according to RECIST 1.1 within 28 days prior to the
             first dose of study treatment. For subjects with only 1 measurable lesion and prior
             radiotherapy, the lesion must be outside the field of prior radiotherapy or must have
             documented progression following radiation therapy.

          -  Subject's tumor sample has CLDN18.2 expression (defined as moderate to strong
             membranous staining by central IHC testing) as follows:

               -  Cohorts 1A and 2: CLDN18.2 high expression (≥ 75% of tumor cells)

               -  Cohort 1B: CLDN18.2 high or intermediate expression (≥ 50% of tumor cells)

          -  Cohorts 1A and 1B Only:

               -  Subject has disease progression on or after at least 2 prior regimens for their
                  advanced disease, including fluoropyrimidine and platinum-containing
                  chemotherapy, and if appropriate, HER2/neu-targeted therapy.

          -  Cohort 2 Only:

               -  Subject has not received prior systemic anti-cancer therapy for their advanced
                  disease (subject may have received neoadjuvant and/or fluorouracil-containing
                  adjuvant chemotherapy as long as it has been completed ≥ 6 months before the
                  first dose of study treatment).

               -  Subject has a gastric or GEJ tumor that is HER2-negative as determined by local
                  or central testing.

          -  Cohorts 1A and 2:

               -  Subject must have an additional available tumor specimen collected within 3
                  months prior to the first dose of study treatment.

               -  Subject is an appropriate candidate for a tumor biopsy and is amenable to undergo
                  a tumor biopsy during the screening period (if applicable) and treatment period.

          -  Subject agrees not to participate in another interventional study while on treatment.

          -  Subject has ECOG performance status 0 to 1.

          -  Subject has predicted life expectancy ≥ 12 weeks.

          -  Subject must meet all of the following criteria on the laboratory tests that will be
             analyzed centrally within 14 days prior to the first dose of study treatment. In case
             of multiple laboratory data within this period, the most recent data should be used.

               -  Hemoglobin (Hgb) ≥ 9 g/dL (no transfusion within 7 days of start of study
                  treatment)

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

               -  Platelets ≥ 100 x 10^9/L

               -  Albumin ≥ 2.5 g/dL

               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
                  without liver metastases (≤ 5 x ULN if liver metastases are present)

               -  Serum creatinine ≤ 1.5 x ULN, or estimated glomerular filtration rate ≥ 45
                  mL/min/1.73 m^2 if creatinine is > ULN

               -  Prothrombin time (PT)/international normalized ratio (INR) and partial
                  thromboplastin time (PTT) ≤ 1.5 x ULN (except for patients receiving
                  anticoagulation therapy)

        Exclusion Criteria:

          -  Subject has had prior severe allergic reaction or intolerance to a monoclonal
             antibody, including humanized or chimeric antibodies.

          -  Subject has known immediate or delayed hypersensitivity or contraindication to any
             component of study treatment.

          -  Subject has received other investigational agents or devices concurrently or within 28
             days prior to first dose of study treatment.

          -  Subject has received systemic immunosuppressive therapy, including systemic
             corticosteroids 14 days prior to first dose of study treatment. Subjects using a
             physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30
             mg per day of hydrocortisone or up to 10 mg per day of prednisone) are allowed.

          -  Subject has gastric outlet syndrome or persistent recurrent vomiting.

          -  Subject with recent gastric bleeding or symptomatic subjects with proven gastric
             ulcers that would preclude the subject from participation.

          -  Subject has known active central nervous system metastases and/or carcinomatous
             meningitis.

          -  Subject has a known history of a positive test for human immunodeficiency virus (HIV)
             infection or known active hepatitis B (positive hepatitis B surface antigen [HBsAg])
             or hepatitis C infection. Subjects who are negative for HBsAg, but hepatitis B core
             antibody positive, will have a hepatitis B DNA test performed and if positive will be
             excluded. Subjects with positive serology, but negative hepatitis C virus RNA test
             results, are eligible.

          -  Subject has had within 6 months prior to first dose of study treatment any of the
             following: unstable angina, myocardial infarction, ventricular arrhythmia requiring
             intervention or hospitalization for heart failure.

          -  Subject has active infection requiring systemic therapy.

          -  Subject has active autoimmune disease that has required systemic treatment in the past
             2 years.

          -  Subject has a clinically significant disease or co-morbidity that may adversely affect
             the safe delivery of treatment within this study or make the subject unsuitable for
             study participation.

          -  Subject has psychiatric illness or social situations that would preclude study
             compliance.

          -  Subject has had a major surgical procedure without complete recovery within 28 days
             before start of study treatment.

          -  Subject has had radiotherapy within 14 days (Cohort 1) and within 28 days (Cohort 2)
             prior to start of study treatment. Subject who received palliative radiotherapy to
             peripheral bone metastases within 14 days prior to start of study treatment and has
             recovered from all acute toxicities is allowed.

          -  Subject has another past or active malignancy, which is likely to require treatment.

          -  Cohort 2 Only, subject has:

               -  Prior severe allergic reaction or intolerance to any component of mFOLFOX6
                  chemotherapeutics in this study

               -  Known dihydropyrimidine dehydrogenase deficiency

               -  Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the
                  sole neurological abnormality does not render the subject ineligible).

               -  Sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if
                  present, should be stable or improving.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) of IMAB362 as a single agent by central review (Cohort 1)
Time Frame:Up to 3 months
Safety Issue:
Description:The ORR is defined as the proportion of participants with complete or partial objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 (assessed by an independent review committee (IRC)).

Secondary Outcome Measures

Measure:Pharmacokinetics (PK) of IMAB362: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCinf will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity Percentage (AUCinf (%extrap)) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCinf (%extrap) will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUClast will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Area Under the Concentration-Time Curve from the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCtau will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Maximum Concentration (Cmax) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Cmax will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Concentration Immediately Prior to Dosing (Ctrough) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Ctrough will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Time of Maximum Concentration (Tmax) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Tmax will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Apparent Terminal Elimination Half-life (T1/2) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:T1/2 will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Time of the last measurable concentration (Tlast) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Tlast will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Clearance (CL) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:CL will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Apparent Volume of Distribution at Steady State (Vss) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Vss will be derived from the PK serum samples collected.
Measure:PK of IMAB362: Apparent Volume of Distribution During the Terminal Phase (Vz) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Vz will be derived from the PK serum samples collected.
Measure:PK of oxaliplatin: AUCinf (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCinf will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: AUCinf (%extrap) (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCinf (%extrap) will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: AUClast (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUClast will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: AUCtau (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCtau will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: Cmax (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Cmax will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: Ctrough (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Ctrough will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: Tmax (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Tmax will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: T1/2 (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:T1/2 will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: Tlast (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Tlast will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: CL (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:TL will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: Vss (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Vss will be derived from the PK plasma samples collected.
Measure:PK of oxaliplatin: Vz (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Vz will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): AUCinf (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCinf will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): AUCinf (%extrap) (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCinf (%extrap) will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): AUClast (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUClast will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): AUCtau (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:AUCtau will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): Cmax (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Cmax will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): Ctrough (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Ctrough will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): Tmax (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Tmax will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): T1/2 (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:T1/2 will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): Tlast (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Tlast will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): CL (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:CL will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): Vss (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Vss will be derived from the PK plasma samples collected.
Measure:PK of fluorouracil bolus (5-FU): Vz (Cohort 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Vz will be derived from the PK plasma samples collected.
Measure:Safety and tolerability assessed by adverse events (AEs) (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measure:Number of participants with electrocardiogram (ECG) abnormalities and or adverse events (Cohorts 1 and 2)
Time Frame:Up to 14 months
Safety Issue:
Description:Number of participants with potentially clinically significant ECG values.
Measure:Number of participants with vital signs abnormalities and or adverse events (Cohorts 1 and 2)
Time Frame:Up to 14 months
Safety Issue:
Description:Number of participants with potentially clinically significant vital sign values.
Measure:Number of participants with European Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events (Cohorts 1 and 2)
Time Frame:Up to 14 months
Safety Issue:
Description: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.
Measure:Number of participants with laboratory assessments abnormalities and or adverse events (Cohorts 1 and 2)
Time Frame:Up to 14 months
Safety Issue:
Description:Number of participants with potentially clinically significant laboratory values.
Measure:Changes in tumor expression of CLDN18.2 (Cohorts 1 and 2)
Time Frame:Up to 1.5 months
Safety Issue:
Description:Fold change in CLDN18.2 expression with treatment as determined by immunohistochemistry (IHC) staining of pre and on treatment Formalin Fixed Paraffin Embedded (FFPE) tumor tissue samples.
Measure:Changes in immune related biomarkers in tumor tissue: Thymus (T) cells (Cohorts 1 and 2)
Time Frame:Up to 1.5 months
Safety Issue:
Description:Fold change in levels of T cells with treatment as determined by immunohistochemistry (IHC) staining of tumor tissue samples. T cell population levels will be analyzed.
Measure:Changes in immune related biomarkers in tumor tissue: Natural Killer (NK) cells (Cohorts 1 and 2)
Time Frame:Up to 1.5 months
Safety Issue:
Description:Fold change in levels of NK cells with treatment as determined by IHC staining of tumor tissue samples. NK cell population levels will be analyzed.
Measure:Changes in immune related biomarkers in tumor tissue: Monocytes (Cohorts 1 and 2)
Time Frame:Up to 1.5 months
Safety Issue:
Description:Fold change in levels of monocytes with treatment as determined by IHC staining of tumor tissue samples. Monocyte population levels will be analyzed.
Measure:Changes in immune related biomarkers in tumor tissue: Macrophages (Cohorts 1 and 2)
Time Frame:Up to 1.5 months
Safety Issue:
Description:Fold change in levels of macrophages with treatment as determined by IHC staining of tumor tissue samples. Macrophage population levels will be analyzed.
Measure:Changes in immune related biomarkers in blood samples: T cells (Cohorts 1 and 2)
Time Frame:Up to 6 months
Safety Issue:
Description:Fold change in levels of T cells with treatment as determined by flow cytometry of blood samples. T cell population levels will be analyzed.
Measure:Changes in immune related biomarkers in blood samples: NK cells (Cohorts 1 and 2)
Time Frame:Up to 6 months
Safety Issue:
Description:Fold change in levels of NK cells with treatment as determined by flow cytometry of blood samples. NK cell population levels will be analyzed.
Measure:Changes in immune related biomarkers in blood samples: Monocytes (Cohorts 1 and 2)
Time Frame:Up to 6 months
Safety Issue:
Description:Fold change in levels of monocytes with treatment as determined by flow cytometry of blood samples. Monocyte population levels will be analyzed.
Measure:Changes in immune related biomarkers in blood samples: Macrophages (Cohorts 1 and 2)
Time Frame:Up to 6 months
Safety Issue:
Description:Fold change in levels of macrophages with treatment as determined by flow cytometry of blood samples. Macrophage population levels will be analyzed.
Measure:Number of anti-drug antibody (ADA) Positive Participants (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Immunogenicity will be measured by the number of participants that are ADA positive.
Measure:Health Related Quality of Life (HRQoL) measured by the Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) questionnaire (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:The EORTC-QLQ-C30 is a cancer-specific instrument consisting of 5 functional domain scales: physical, role, emotional, social and cognitive.
Measure:HRQoL measured by the Oesophago-Gastric Module (EORTC QLQ-OG-25) questionnaire (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:The EORTC-QLQ-OG25 instrument evaluates GC- and GEJC-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion.
Measure:HRQoL measured by the Global Pain (GP) questionnaire (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:The GP instrument is a single assessment of overall pain.
Measure:HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
Measure:HRQoL measured by the Health Resource Utilization (HRU) questionnaire (Cohorts 1 and 2)
Time Frame:Up to 16 months
Safety Issue:
Description:Health resource utilization questionnaire to assess the number of office visits, hospital stays and other healthcare resource utilization that occur outside of the clinical trial.
Measure:Disease Control Rate (DCR) of IMAB362 as a single agent by central review (Cohort 1)
Time Frame:Up to 3 months
Safety Issue:
Description:The DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
Measure:Duration of Response (DOR) of IMAB362 as a single agent by central review (Cohort 1)
Time Frame:Up to 3 months
Safety Issue:
Description:DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measure:Progression Free Survival (PFS) of IMAB362 as a single agent by central review (Cohort 1)
Time Frame:Up to 3 months
Safety Issue:
Description:PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.
Measure:Overall Survival (OS) of IMAB362 as a single agent by central review (Cohort 1)
Time Frame:Up to 7 months
Safety Issue:
Description:OS is defined as the time from the date of treatment start until the documented date of death from any cause.
Measure:ORR of IMAB362 in combination with mFOLFOX6 by central review (Cohort 2)
Time Frame:Up to 13 months
Safety Issue:
Description:The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
Measure:PFS of IMAB362 in combination with mFOLFOX6 by central review (Cohort 2)
Time Frame:Up to 13 months
Safety Issue:
Description:PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • oxaliplatin
  • fluorouracil
  • IMAB362
  • Gastro-Esophageal Junction cancer
  • Gastric cancer

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