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Study of BAY1834942 in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03596372
Recruitment Status : Recruiting
First Posted : July 23, 2018
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:

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 tumor type-specific expansion in which BAY1834942 will be administered either alone (monotherapy) or in combination with pembrolizumab (combination therapy).


Condition or disease Intervention/treatment Phase
Advanced CEACAM6-expressing Solid Tumors Drug: BAY1834942 Drug: BAY1834942 + Pembrolizumab Phase 1

Detailed Description:

The primary objectives of the study are to evaluate and characterize the tolerability and safety profile of repeated doses of BAY1834942 alone or in combination with pembrolizumab, and to characterize the pharmacokinetics of BAY1834942 alone or in combination with pembrolizumab after single dose.

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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 296 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : June 15, 2021
Estimated Study Completion Date : December 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Patients with Solid tumors_Monotherapy

Escalation cohorts:

On Day 1 of each 21-day cycle, patients receive escalating doses of BAY1834942 intravenously for 1 hour.

Drug: BAY1834942

Dose escalation:

Sequential dose levels of 2.5, 10, 30, 100, 300, 600, 1200 and 1800 mg

.

Dose expansion:

With maximum tolerated dose (MTD) identified in dose escalation part or with 1800 mg dose, if tolerated.

Other Name: Anti-CEACAM6 antibody

Experimental: Patients with Solid tumors_Combination therapy

Escalation cohorts:

On Day 1 of each 21-day cycle, patients receive escalating doses of BAY1834942 intravenously for 1 hour and pembrolizumab intravenously for 30 minutes.

Drug: BAY1834942 + Pembrolizumab

Dose escalation Sequential dose levels potentially of 600, 1200 and 1800 mg of BAY1834942 in combination with 200 mg pembrolizumab

Dose expansion With maximum tolerated dose of BAY1834942 (MTD) identified in dose escalation part of combination therapy or with 1800 mg BAY1834942 dose, if tolerated

Other Names:
  • BAY1834942: Anti-CEACAM6 antibody
  • Pembroluzimab: immunoglobulin G4 monoclonal antibody; Keytruda

Experimental: Patients with Gastric cancer_Monotherapy

Expansion cohort with patients having gastric and/or gastroesophageal adenocarcinoma:

On Day 1 of each 21-day cycle, patients receive BAY1834942 intravenously for 1 hour.

Drug: BAY1834942

Dose escalation:

Sequential dose levels of 2.5, 10, 30, 100, 300, 600, 1200 and 1800 mg

.

Dose expansion:

With maximum tolerated dose (MTD) identified in dose escalation part or with 1800 mg dose, if tolerated.

Other Name: Anti-CEACAM6 antibody

Experimental: Patients with Gastric cancer_Combination therapy

Expansion cohort with patients having gastric and/or gastroesophageal adenocarcinoma:

On Day 1 of each 21-day cycle, patients receive BAY1834942 intravenously for 1 hour and pembrolizumab intravenously for 30 minutes.

Drug: BAY1834942 + Pembrolizumab

Dose escalation Sequential dose levels potentially of 600, 1200 and 1800 mg of BAY1834942 in combination with 200 mg pembrolizumab

Dose expansion With maximum tolerated dose of BAY1834942 (MTD) identified in dose escalation part of combination therapy or with 1800 mg BAY1834942 dose, if tolerated

Other Names:
  • BAY1834942: Anti-CEACAM6 antibody
  • Pembroluzimab: immunoglobulin G4 monoclonal antibody; Keytruda

Experimental: Patients with Colorectal cancer_Monotherapy

Expansion cohort with patients having colorectal cancer:

On Day 1 of each 21-day cycle, patients receive BAY1834942 intravenously for 1 hour.

Drug: BAY1834942

Dose escalation:

Sequential dose levels of 2.5, 10, 30, 100, 300, 600, 1200 and 1800 mg

.

Dose expansion:

With maximum tolerated dose (MTD) identified in dose escalation part or with 1800 mg dose, if tolerated.

Other Name: Anti-CEACAM6 antibody

Experimental: Patients with Colorectal cancer_Combination therapy

Expansion cohort with patients having colorectal cancer:

On Day 1 of each 21-day cycle, patients receive BAY1834942 intravenously for 1 hour and pembrolizumab intravenously for 30 minutes.

Drug: BAY1834942 + Pembrolizumab

Dose escalation Sequential dose levels potentially of 600, 1200 and 1800 mg of BAY1834942 in combination with 200 mg pembrolizumab

Dose expansion With maximum tolerated dose of BAY1834942 (MTD) identified in dose escalation part of combination therapy or with 1800 mg BAY1834942 dose, if tolerated

Other Names:
  • BAY1834942: Anti-CEACAM6 antibody
  • Pembroluzimab: immunoglobulin G4 monoclonal antibody; Keytruda

Experimental: Patients with Non-small-cell-lung cancer_Monotherapy

Expansion cohort with patients having adeno Non-small-cell-lung cancer:

On Day 1 of each 21-day cycle, patients receive BAY1834942 intravenously for 1 hour.

Drug: BAY1834942

Dose escalation:

Sequential dose levels of 2.5, 10, 30, 100, 300, 600, 1200 and 1800 mg

.

Dose expansion:

With maximum tolerated dose (MTD) identified in dose escalation part or with 1800 mg dose, if tolerated.

Other Name: Anti-CEACAM6 antibody

Experimental: Patients with Non-small-cell-lung cancer_Combination therapy

Expansion cohort with patients having adeno Non-small-cell-lung cancer:

On Day 1 of each 21-day cycle, patients receive BAY1834942 intravenously for 1 hour and pembrolizumab intravenously for 30 minutes.

Drug: BAY1834942 + Pembrolizumab

Dose escalation Sequential dose levels potentially of 600, 1200 and 1800 mg of BAY1834942 in combination with 200 mg pembrolizumab

Dose expansion With maximum tolerated dose of BAY1834942 (MTD) identified in dose escalation part of combination therapy or with 1800 mg BAY1834942 dose, if tolerated

Other Names:
  • BAY1834942: Anti-CEACAM6 antibody
  • Pembroluzimab: immunoglobulin G4 monoclonal antibody; Keytruda




Primary Outcome Measures :
  1. Incidence of Treatment-emergent adverse events [ Time Frame: Up to 40 months ]
  2. Severity of Treatment-emergent adverse events [ Time Frame: Up to 40 months ]
    Using the Common Terminology Criteria for Adverse Events (CTCAE) scale

  3. AUC(0-504) of BAY1834942 after single dose [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 168, 336 and 504 hours after drug in Cycle 1 (cycle length is 21 days) ]
    Area under the plasma concentration curve of drug from 0 to 504 hours after single dose

  4. Cmax of BAY1834942 after single dose [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 168, 336 and 504 hours after drug in Cycle 1 (cycle length is 21 days) ]
    Maximum plasma concentration of drug after single dose


Secondary Outcome Measures :
  1. AUC(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 hours in Cycle 3 (cycle length is 21 days) ]
    Area under the plasma concentration curve of drug from 0 to 504 hours after multiples doses

  2. 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 hours in Cycle 3 (cycle length is 21 days) ]
    Maximum plasma concentration of drug after multiples doses

  3. Overall response rate (ORR) [ Time Frame: Up to 40 months ]
    Percentage of patients whose best response to BAY1834942 is either a Complete response or Partial response, both defined according to RECIST criteria

  4. Leukocyte immune phenotyping [ Time Frame: On Day 1 (pre-dose), 24, 48, 168 and 336 hours after drug of Cycle 1 (cycle length is 21 days); 0 (pre-dose) and 168 hours after drug of Cycle 2; 0 hour (pre-dose) of Cycles 3, 4, 6 and 8; 1 Day of End of treatment ]
    Whole blood flow cytometry (FACS) for characterization of blood leukocytes/ lymphocytes with regard to subpopulations, differentiation and activation before, under and after treatment in all patients

  5. CEACAM6 receptor occupancy [ Time Frame: On Day 1 (pre-dose), 24, 168 and 336 hours after drug of Cycle 1 (cycle length is 21 days); 0 hour (pre-dose) of Cycle 2 ]
    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 for dose escalation cohorts 10, 30, 100 and 300 mg BAY1834942

  6. Cytokine level [ Time Frame: On Day 1 (pre-dose), 6, 24, 48, 168 and 336 hours after drug of Cycle 1 (cycle length is 21 days); 0 (pre-dose) and 168 hours after drug of Cycle 2; 0 hour (pre-dose) of Cycles 3, 4, 6 and 8; 1 Day of End of treatment ]
    Total concentration of proinflammatory and immunostimulatory cytokines in plasma

  7. Ex vivo-stimulated cytokine secretion [ Time Frame: On Day 1 (pre-dose), 24, 48, 168 and 336 hours after drug of Cycle 1 (cycle length is 21 days); 0 (pre-dose) and 168 hours after drug of Cycle 2; 0 hour (pre-dose) of Cycles 3, 4, 6 and 8; 1 Day of End of treatment ]
    Total concentration of selected proinflammatory and immunostimulatory cytokines in culture plasma after ex-vivo stimulation of whole blood taken before, under and after treatment in all patients

  8. Concentration of carcinoembryonic antigens (CEA; tumor marker) in blood [ Time Frame: On Day 1 (pre-dose) of Cycle 1; 0 hour (pre-dose) of Cycles 2, 3, 4, 6, 8 (cycle length is 21 days), and on 1 Day of End of treatment ]

Other Outcome Measures:
  1. 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 ]
    Concentration in plasma



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 of (non-infectious) pneumonitis that required steroids or current 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03596372


Contacts
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Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com

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Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03596372     History of Changes
Other Study ID Numbers: 18650
2018-002561-19 ( EudraCT Number )
First Posted: July 23, 2018    Key Record Dates
Last Update Posted: June 24, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
First-in-human
Immuno-oncology
CEACAM6
Checkpoint Inhibition
Monotherapy
Combination therapy
Pembrolizumab

Additional relevant MeSH terms:
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Antibodies
Immunoglobulins
Immunoglobulin G
Pembrolizumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents