Advanced CEACAM6-expressing Solid Tumors Clinical Trial
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
| Verified date | May 2022 |
| Source | Bayer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 30 |
| Est. completion date | February 22, 2021 |
| Est. primary completion date | November 16, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Princess Margaret Hospital-University Health Network | Toronto | Ontario |
| Singapore | National University Hospital | Singapore | |
| United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| Lead Sponsor | Collaborator |
|---|---|
| Bayer |
United States, Canada, Singapore,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence of treatment-emergent adverse events | Up to 40 months | ||
| Primary | Severity of treatment-emergent adverse events | Using the Common Terminology Criteria for Adverse Events (CTCAE) scale | Up to 40 months | |
| Primary | Cmax of BAY1834942 after single dose | Maximum plasma concentration of drug 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) | |
| Primary | AUC(0-504) of BAY1834942 after single dose | Area under the plasma concentration curve of drug from 0 to 504 hours 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) | |
| Secondary | AUC(0-504),md of BAY1834942 after multiple doses | Area under the plasma concentration curve of drug from 0 to 504 hours after multiples 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) | |
| Secondary | Cmax,md of BAY1834942 after multiple doses | Maximum plasma concentration of drug after multiples 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) | |
| Secondary | Overall response rate (ORR) | Percentage of patients whose best response to BAY1834942 is either a Complete response or Partial response, both defined according to RECIST criteria | Up to 40 months | |
| Secondary | Leukocyte immune phenotyping | 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 | 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 | |
| Secondary | CEACAM6 receptor occupancy | 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 | 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 | |
| Secondary | Cytokine levels | 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 | 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 | |
| Secondary | Ex vivo-stimulated cytokine secretion | 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 | 0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days) | |
| Secondary | Concentration of carcinoembryonic antigens (CEA; tumor marker) in serum | Total concentration of CEA in serum derived from whole blood taken before and under treatment in all patients | 0 h (pre-dose) on Day 1 of Cycles 1, 2, 3, 4, 6 and 8 (cycle length is 21 days) | |
| Secondary | Concentration of anti-drug antibodies | Concentration in plasma | 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 |