Study of BAY1834942 in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT03596372
• Recruitment Status: Completed
• First Posted: July 23, 2018
• Last Update Posted: June 2, 2022
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced CEACAM6-expressing Solid Tumors	Drug: BAY1834942	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 19, 2018
• Actual Primary Completion Date: November 16, 2020
• Actual Study Completion Date: February 22, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: BAY1834942; Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.; Other Name: Anti-CEACAM6 antibody
Experimental: 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.	Drug: BAY1834942; Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.; Other Name: Anti-CEACAM6 antibody
Experimental: 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.	Drug: BAY1834942; Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.; Other Name: Anti-CEACAM6 antibody
Experimental: 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.	Drug: BAY1834942; Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.; Other Name: Anti-CEACAM6 antibody
Experimental: 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).	Drug: BAY1834942; Dose escalation: Sequential dose levels . Dose expansion (except for low-dose expansion): With maximum tolerated dose (MTD) identified in dose escalation part.; Other Name: Anti-CEACAM6 antibody

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events [ Time Frame: Up to 40 months ]
2. Severity of treatment-emergent adverse events [ Time Frame: Up to 40 months ]
   Using the Common Terminology Criteria for Adverse Events (CTCAE) scale
3. 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
4. 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

Secondary Outcome Measures :

1. 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) ]
   Area under the plasma concentration curve of drug from 0 to 504 hours after multiples doses.
2. 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) ]
   Maximum plasma concentration of drug after multiples doses
3. Overall response rate (ORR) [ Time Frame: 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
4. 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 ]
   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
5. 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 ]
   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
6. 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 ]
   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
7. 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) ]
   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
8. 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) ]
   Total concentration of CEA in serum derived from whole blood taken before and under treatment in all patients
9. 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 ]
   Concentration in plasma

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Canada, Ontario

Princess Margaret Hospital-University Health Network

Toronto, Ontario, Canada, M5G 2M9

Singapore

National University Hospital

Singapore, Singapore, 119074

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here to find results for studies related to Bayer products 

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03596372
• Other Study ID Numbers: 18650; 2018-002561-19 ( EudraCT Number )
• First Posted: July 23, 2018
• Last Update Posted: June 2, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:

First-in-human; Immuno-oncology; CEACAM6; Checkpoint inhibition

Additional relevant MeSH terms:

Neoplasms