Clinical trial NCT03596372: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced CEACAM6-expressing Solid Tumors
Keywords: First-in-human
Immuno-oncology
CEACAM6
Checkpoint inhibition
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 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.

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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: Up to 40 months
measure: Severity of treatment-emergent adverse events
timeFrame: Up to 40 months
measure: Cmax of BAY1834942 after single dose
timeFrame: 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)
measure: AUC(0-504) of BAY1834942 after single dose
timeFrame: 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)
Secondary outcomes:
measure: AUC(0-504),md of BAY1834942 after multiple doses
timeFrame: 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)
measure: Cmax,md of BAY1834942 after multiple doses
timeFrame: 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)
measure: Overall response rate (ORR)
timeFrame: Up to 40 months
measure: Leukocyte immune phenotyping
timeFrame: 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
measure: CEACAM6 receptor occupancy
timeFrame: 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
measure: Cytokine levels
timeFrame: 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
measure: Ex vivo-stimulated cytokine secretion
timeFrame: 0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days)
measure: Concentration of carcinoembryonic antigens (CEA; tumor marker) in serum
timeFrame: 0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days)
measure: Concentration of anti-drug antibodies
timeFrame: 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
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Hospital-University Health Network
state: Ontario
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: