Study of BAY1834942 in Patients With Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced CEACAM6-expressing Solid Tumors

Intervention / Treatment
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* Drug: BAY1834942


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with Solid tumors<br>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. | Drug: BAY1834942<br>* Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.<br>* Other names: Anti-CEACAM6 antibody;|
| Experimental: Patients with Gastric cancer<br>Expansion with patients having gastric and/or gastroesophageal adenocarcinoma: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part. | Drug: BAY1834942<br>* Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.<br>* Other names: Anti-CEACAM6 antibody;|
| Experimental: Patients with Colorectal cancer<br>Expansion with patients having colorectal cancer: Patients receive BAY1834942 intravenously for 1 hour according to dosing scheme decided in escalation part. | Drug: BAY1834942<br>* Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.<br>* Other names: Anti-CEACAM6 antibody;|
| Experimental: Patients with Non-small-cell-lung cancer<br>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. | Drug: BAY1834942<br>* Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.<br>* Other names: Anti-CEACAM6 antibody;|
| Experimental: Low-dose expansion<br>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). | Drug: BAY1834942<br>* Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.<br>* Other names: Anti-CEACAM6 antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events |  | Up to 40 months | 
| Severity of treatment-emergent adverse events | Using the Common Terminology Criteria for Adverse Events (CTCAE) scale | Up to 40 months | 
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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) | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-in-human, Immuno-oncology, CEACAM6, Checkpoint inhibition