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
Overview
- Phase
- Phase 1
- Intervention
- BAY1834942
- Conditions
- Advanced CEACAM6-expressing Solid Tumors
- Sponsor
- Bayer
- Enrollment
- 30
- Locations
- 4
- Primary Endpoint
- Incidence of treatment-emergent adverse events
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
- •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
Arms & Interventions
Patients with Solid tumors
Dose 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.
Intervention: BAY1834942
Patients with Gastric cancer
Expansion with patients having gastric and/or gastroesophageal adenocarcinoma: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part.
Intervention: BAY1834942
Patients with Colorectal cancer
Expansion with patients having colorectal cancer: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part.
Intervention: BAY1834942
Patients with Non-small-cell-lung cancer
Expansion with patients having adeno Non-small-cell-lung cancer: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part.
Intervention: BAY1834942
Low-dose expansion
Expansion 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).
Intervention: BAY1834942
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events
Time Frame: Up to 40 months
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
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
Severity of treatment-emergent adverse events
Time Frame: Up to 40 months
Using the Common Terminology Criteria for Adverse Events (CTCAE) scale
Secondary Outcomes
- AUC(0-504),md of BAY1834942 after multiple doses(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))
- Cmax,md of BAY1834942 after multiple doses(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))
- Overall response rate (ORR)(Up to 40 months)
- Leukocyte immune phenotyping(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)
- CEACAM6 receptor occupancy(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)
- Concentration of carcinoembryonic antigens (CEA; tumor marker) in serum(0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days))
- Concentration of anti-drug antibodies(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)
- Cytokine levels(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)
- Ex vivo-stimulated cytokine secretion(0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days))