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A First-in-human Study of ILDR2 (Immunoglobulin-like Domain Containing Receptor 2) Function-blocking Antibody BAY1905254

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ClinicalTrials.gov Identifier: NCT03666273
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : January 11, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
The main purpose of this clinical study is to determine the most appropriate dose of the study medication that can be safely given to subjects, and to look at how the study medication is changed and distributed by the body.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: BAY1905254 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 196 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, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Tumor Response Profile of the ILDR2 Function-blocking Antibody BAY1905254 in Patients With Advanced Solid Tumors
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : July 14, 2023
Estimated Study Completion Date : July 14, 2023

Arm Intervention/treatment
Experimental: Dose escalation
Patients with solid tumor types considered immunosensitive
Drug: BAY1905254
Intravenous (i.v.) application of study drug every 2-3 weeks in a predefined dose escalation scheme.

Experimental: Tumor type-specific expansion
Patients with urothelial cancer, Head and neck squamous cell carcinoma (HNSCC) and cervical cancer
Drug: BAY1905254
i.v. application of study drug at the MTD (Maximum tolerated dose) to determine the RP2D (Recommended Phase 2 dose)




Primary Outcome Measures :
  1. The incidence of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs) and adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs) [ Time Frame: Up to 2 years ]
  2. The severity of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs) and adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs) [ Time Frame: Up to 2 years ]
  3. Cmax of BAY1905254 after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 96, 168, 264, 336 and (504) hours after drug in Cycle 1 ]
    Maximum plasma concentration after single dose

  4. AUC (of the respective dosing interval) of BAY1905254 after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 96, 168, 264, 336 and (504) hours after drug in Cycle 1 ]
    Area under the plasma concentration curve from 0 to 336 hours after single dose (Q2W(every 2 weeks) only); Area under the plasma concentration curve from 0 to 504 hours after single dose (Q3W (every 3 weeks) only)


Secondary Outcome Measures :
  1. Cmax,md of the respective dosing interval after multiple dosing in Cycle 3 Day 1 for cohorts receiving doses ≥ 20 mg [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 96, 168, 264, 336 and (504) hours after drug in Cycle 3 ]
    Maximum plasma concentration after multiple doses

  2. AUC of the respective dosing interval after multiple dosing in Cycle 3 Day 1 for cohorts receiving doses ≥ 20 mg [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 96, 168, 264, 336 and (504) hours after drug in Cycle 3 ]
    Area under the plasma concentration curve from 0 to 336 hours after multiple doses (Q2W only); Area under the plasma concentration curve from 0 to 504 hours after multiple doses (Q3W only)

  3. Best overall response rate (BORR) [ Time Frame: Up to 2 years ]
  4. Incidence of positive anti-drug antibody and neutralizing antibody titer [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Patients with following histologically confirmed, advanced solid tumors are eligible:

    • Dose escalation: all solid tumor types with a likelihood of sensitivity to immunotherapy, as judged by the investigator.
    • Tumor type-specific high-dose (at MTD or MAD(Maximum administered dose)) expansion cohorts: urothelial cancer, HNSCC and cervical cancer.

      --- TMB (Tumor mutational burden) enrichment phase only: each tumor type-specific expansion cohort will be enriched with at least 6 patients with medium-to-high TMB (≥ 10 mutations/Mb).

    • Tumor type-specific low-dose expansion cohort (optional): any tumor type based on data from dose escalation and expansion indicating pharmacodynamics effect.
  • Provision of archival tumor tissue at screening is mandatory.
  • Patients must have received standard therapy or have no standard therapy available or patients have actively refused any treatment which would be regarded standard. Or, in the opinion of investigator have been considered ineligible for a particular form of standard therapy on medical grounds.
  • Adequate bone marrow, liver and renal function.
  • Adequate cardiac function, measured by echocardiography.
  • All dose expansion cohorts: willingness to undergo paired biopsy of tumor.

Exclusion Criteria:

  • History of severe immune related adverse effects from prior immunotherapy (CTCAE v.5.0 Grade 4; CTCAE v.5.0 Grade 3 requiring treatment > 4 weeks), except hypothyroidism clinically stable on hormone replacement treatment and controlled type 1 diabetes.
  • Severe (CTCAE v.5.0 Grade ≥ 3) infections within 4 weeks before the first study drug administration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Clinically active infections (CTCAE v.5.0 > Grade 1) within 2 weeks before the first study drug administration.
  • Previous or active myocarditis/myositis in history (independent of cause)
  • Active or history of autoimmune disease.
  • Known human immunodeficiency virus (HIV) infection.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • Treatment with systemic immunosuppressant medications within 2 weeks before the first study drug administration.
  • Ongoing or previous anti-cancer treatment or any immunostimulatory treatment including but not limited to interferons (IFNs), interleukin (IL)-2 and agonists for members of the tumor necrosis factor (TNF) receptor superfamily (e.g. 4-1BB) within 4 weeks before the first study drug administration. Prior treatment with other immune-checkpoint inhibitors is acceptable if patients are in disease progression according to response evaluation criteria in solid tumors (RECIST) 1.1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03666273


Contacts
Contact: Bayer Clinical Trials Contact (+)1-888-8422937 clinical-trials-contact@bayer.com

Locations
United States, California
University of Southern California Not yet recruiting
Los Angeles, California, United States, 90033
United States, Connecticut
Yale University School of Medicine Not yet recruiting
New Haven, Connecticut, United States, 06510
United States, Illinois
University of Chicago Hospitals Recruiting
Chicago, Illinois, United States, 60637
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
United States, Texas
Texas Oncology, PA Not yet recruiting
Dallas, Texas, United States, 75246
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03666273     History of Changes
Other Study ID Numbers: 18789
2018-000990-63 ( EudraCT Number )
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019

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

Keywords provided by Bayer:
Neoplasm
Immuno oncology drug

Additional relevant MeSH terms:
Antibodies
Antibodies, Blocking
Immunologic Factors
Physiological Effects of Drugs