Advanced CEACAM6-expressing Solid Tumors
Conditions
Keywords
First-in-human, Immuno-oncology, CEACAM6, Checkpoint inhibition
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.
Interventions
DRUGBAY1834942
Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | Up to 40 months | — |
| Severity of treatment-emergent adverse events | Up to 40 months | Using the Common Terminology Criteria for Adverse Events (CTCAE) scale |
| Cmax of BAY1834942 after single dose | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| 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 | 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 |
| 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) | Area under the plasma concentration curve of drug from 0 to 504 hours after multiples doses. |
| 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) | Total concentration of CEA in serum derived from whole blood taken before and under treatment in all patients |
| 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 | Concentration in plasma |
| 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) | 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 |
| 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) | Maximum plasma concentration of drug after multiples doses |
| Overall response rate (ORR) | 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 |
| 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 | 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 |
Countries
Canada, Singapore, United States
Outcome results
None listed