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Completed

NCT Number: NCT03596372

Study of BAY1834942 in Patients With Solid Tumors

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.

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Key information

Conditions

Advanced CEACAM6-expressing Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Princess Margaret Hospital-University Health Network, Toronto, Ontario, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BAY1834942

Drug

Dose escalation:

Sequential dose levels

.

Dose expansion (except for low-dose expansion):

With maximum tolerated dose (MTD) identified in dose escalation part.

Other names: Anti-CEACAM6 antibody

Primary outcomes

  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. 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 h after drug in Cycle 1 (cycle length is 21 days)

    Maximum plasma concentration of drug after single dose

  4. 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 h 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

Secondary outcomes

  1. 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)

    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 h 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: 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

    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

  5. 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

    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

  6. 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

    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

  7. 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)

    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

  8. 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)

    Total concentration of CEA in serum derived from whole blood taken before and under treatment in all patients

  9. 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

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2020
Study completion
2021
First posted
Jul 23, 2018
Registry last updated
Jun 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.