Study of BAY1834942 in Patients With Solid Tumors

Phase 1

Completed

• Conditions: Advanced CEACAM6-expressing Solid Tumors
• Interventions: Drug: BAY1834942

• Registration Number: NCT03596372
• Lead Sponsor: Bayer

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-06-19
• Study First Submitted: 2018-06-26
• Study First Submitted QC: 2018-07-20
• Study First Posted: 2018-07-23
• Primary Completion: 2020-11-16
• Study Completion: 2021-02-22
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-30
• Last Update Posted: 2022-06-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Patients with Solid tumors	BAY1834942	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	BAY1834942	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	BAY1834942	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	BAY1834942	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	BAY1834942	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).

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events	Up to 40 months
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
Severity of treatment-emergent adverse events	Up to 40 months	Using the Common Terminology Criteria for Adverse Events (CTCAE) scale

Secondary Outcome Measures

Name	Time	Method
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.
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
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
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
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
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

Trial Locations

Locations (4)

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Princess Margaret Hospital-University Health Network; 🇨🇦 Toronto, Ontario, Canada

National University Hospital; 🇸🇬 Singapore, Singapore