Clinical Trials /

Study of BAY1834942 in Patients With Solid Tumors

NCT03596372

Description:

This is an open-label, Phase 1, first-in-human, dose escalation and expansion study designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and tumor response profile of the anti-Carcinoembryonic-antigen-related-cell-adhesion-molecule-6 (CEACAM6) antibody BAY1834942 in patients with advanced solid tumors known to have a prevalence for CEACAM6 expression. The study consists of dose escalation and a tumor type-specific expansion.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Bile Duct Carcinoma
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of BAY1834942 in Patients With Solid Tumors
  • Official Title: An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Tumor Response Profile of the Anti-CEACAM6 Antibody BAY1834942 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 18650
  • SECONDARY ID: 2018-002561-19
  • NCT ID: NCT03596372

Conditions

  • Advanced CEACAM6-expressing Solid Tumors

Interventions

DrugSynonymsArms
BAY1834942Anti-CEACAM6 antibodyPatients with Solid tumors

Purpose

This is an open-label, Phase 1, first-in-human, dose escalation and expansion study designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and tumor response profile of the anti-Carcinoembryonic-antigen-related-cell-adhesion-molecule-6 (CEACAM6) antibody BAY1834942 in patients with advanced solid tumors known to have a prevalence for CEACAM6 expression. The study consists of dose escalation and a tumor type-specific expansion.

Detailed Description

      The primary objectives of the study are to evaluate and characterize the tolerability and
      safety profile of repeated doses of BAY1834942, and to characterize the pharmacokinetics of
      BAY1834942 after single dose.

      Secondary objectives are to evaluate the tumor response profile, pharmacodynamics,
      pharmacokinetics and immunogenicity after multiple doses of the drug.
    

Trial Arms

NameTypeDescriptionInterventions
Patients with Solid tumorsExperimentalDose escalation with patients having solid tumors. Patients receive escalating doses of BAY1834942 intravenously for 1 hour on Day 1 of each 21-day cycle (Q3W). If the Q3W scheme does not result in sufficient exposure, the scheme is replaced with an once-weekly (QW) dosing scheme.
  • BAY1834942
Patients with Gastric cancerExperimentalExpansion with patients having gastric and/or gastroesophageal adenocarcinoma: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part.
  • BAY1834942
Patients with Colorectal cancerExperimentalExpansion with patients having colorectal cancer: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part.
  • BAY1834942
Patients with Non-small-cell-lung cancerExperimentalExpansion with patients having adeno Non-small-cell-lung cancer: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part.
  • BAY1834942
Low-dose expansionExperimentalExpansion with patients having the same cancer type (gastric cancer, or colorectal cancer, or non-small-cell lung cancer) and receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part with a dose lower than the maximum tolerated dose (MTD).
  • BAY1834942

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients aged ≥ 18 years

          -  Patients with histologically confirmed advanced/ metastatic solid tumors: Dose
             escalation: solid tumor types with a expression of CEACAM6 (gastric/ GEJ cancer,
             esophageal cancer, NSCLC, CRC, pancreatic cancer, cervical cancer, breast cancer,
             bladder cancer, head and neck squamous cell cancer, bile duct cancer); Dose expansion:
             advanced adeno NSCLC, CRC and gastric/ GEJ adenocarcinoma.

          -  ECOG-PS of 0 to 1.

          -  Adequate organ function (bone marrow, liver, kidneys).

          -  Adequate coagulation function.

          -  Adequate cardiac function

        Exclusion Criteria:

          -  Patients with active symptomatic or untreated brain metastases; possible exceptions
             for patients with treated asymptomatic central nervous system metastases

          -  Active autoimmune disease

          -  History or evidence of active pulmonary fibrosis, organizing pneumonia, or
             pneumonitis.

          -  Risk factors for bowel obstruction or bowel perforation

          -  History of cardiac disease

          -  Uncontrolled arterial hypertension despite optimal medical management

          -  Clinically relevant findings in electrocardiogram

          -  HIV infection

          -  Active HBV or HCV infection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events
Time Frame:Up to 40 months
Safety Issue:
Description:Using the Common Terminology Criteria for Adverse Events (CTCAE) scale

Secondary Outcome Measures

Measure:AUC(0-504),md of BAY1834942 after multiple doses
Time Frame:0 (pre-dose), 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 168, 336 and 504 h in Cycle 3 (cycle length is 21 days)
Safety Issue:
Description:Area under the plasma concentration curve of drug from 0 to 504 hours after multiples doses.
Measure:Cmax,md of BAY1834942 after multiple doses
Time Frame:0 (pre-dose), 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 168, 336 and 504 h in Cycle 3 (cycle length is 21 days)
Safety Issue:
Description:Maximum plasma concentration of drug after multiples doses
Measure:Overall response rate (ORR)
Time Frame:Up to 40 months
Safety Issue:
Description:Percentage of patients whose best response to BAY1834942 is either a Complete response or Partial response, both defined according to RECIST criteria
Measure:Leukocyte immune phenotyping
Time Frame:Screening; 0 (pre-dose), 24, 168, 336 h after drug on Day 1 of Cycle 1 (cycle length is 21 days); 0 (pre-dose), 24, 168 h after drug on Day 1 of Cycle 2; 0 (pre-dose), 24 h after drug on Day 1 of Cycle 3; 0 h (pre-dose) on Day 1 of Cycles 4, 6 and 8
Safety Issue:
Description:Whole blood flow cytometry (FACS) for characterization of blood leukocytes/ lymphocytes with regard to subpopulations, differentiation and activation before and under treatment in all patients
Measure:CEACAM6 receptor occupancy
Time Frame:0 (pre-dose), 24, 168 and 336 h after drug on Day 1 of Cycle 1 (cycle length is 21 days); 0 h (pre-dose) on Day 1 of Cycle 2
Safety Issue:
Description:Total and free CEACAM6 expression levels on blood granulocytes and monocytes as assessed by whole blood flow cytometry (FACS) using 2 different fluorescence-labeled anti-CEACAM6 antibodies either competing or not in CEACAM6 binding with BAY1834942 determined before and under treatment in all dose escalation cohorts
Measure:Cytokine levels
Time Frame:Screen.; 0 (pre-dose), 4, 24, 168, 336 h after drug on Day 1 of Cycle 1 (cycle length 21 days); 0 (pre-dose), 4, 24, 168 h after drug on Day 1 of Cycle 2; 0 (pre-dose), 4, 24 h after drug on Day 1 of Cycle 3; 0 h (pre-dose) on Day 1 of Cycles 4, 6 and 8
Safety Issue:
Description:Total concentration of proinflammatory and immunostimulatory cytokines and of soluble interleukin 2 receptor in serum derived from whole blood taken before and under treatment in all patients
Measure:Ex vivo-stimulated cytokine secretion
Time Frame:0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days)
Safety Issue:
Description:Total concentration of selected proinflammatory and immunostimulatory cytokines in culture plasma after 24 hour ex-vivo stimulation of whole blood taken before and under treatment in all patients
Measure:Concentration of carcinoembryonic antigens (CEA; tumor marker) in serum
Time Frame:0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days)
Safety Issue:
Description:Total concentration of CEA in serum derived from whole blood taken before and under treatment in all patients
Measure:Concentration of anti-drug antibodies
Time Frame:Day 1 (pre-dose) of Cycles 1, 2, 3, 4, 6 and subsequent odd-numbered cycles (cycle length is 21 days); 1 Day of End of treatment; 1 Day of Safety Follow-up visit
Safety Issue:
Description:Concentration in plasma

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • First-in-human
  • Immuno-oncology
  • CEACAM6
  • Checkpoint inhibition

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