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.
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
| Drug | Synonyms | Arms |
|---|
| BAY1834942 | Anti-CEACAM6 antibody | Low-dose expansion |
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
| Name | Type | Description | Interventions |
|---|
| Patients with Solid tumors | Experimental | 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. | |
| Patients with Gastric cancer | Experimental | Expansion with patients having gastric and/or gastroesophageal adenocarcinoma:
Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part. | |
| Patients with Colorectal cancer | Experimental | Expansion with patients having colorectal cancer:
Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part. | |
| Patients with Non-small-cell-lung cancer | Experimental | 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. | |
| Low-dose expansion | Experimental | 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). | |
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: | Completed |
| Lead Sponsor: | Bayer |
Trial Keywords
- First-in-human
- Immuno-oncology
- CEACAM6
- Checkpoint inhibition
Last Updated
April 9, 2021
