Clinical Trials /

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

NCT03666273

Description:

The main purpose of this clinical study is to determine the most appropriate dose of the study medication that can be safely given to cancer patients alone or in combination with another cancer drug, and to look at how the study medication is changed and distributed by the body.

Related Conditions:
  • Cervical Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 18789
  • SECONDARY ID: 2018-000990-63
  • NCT ID: NCT03666273

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
BAY1905254Dose escalation_Monotherapy
BAY1905254 + PembrolizumabDose escalation_Combination therapy

Purpose

The main purpose of this clinical study is to determine the most appropriate dose of the study medication that can be safely given to cancer patients alone or in combination with another cancer drug, and to look at how the study medication is changed and distributed by the body.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation_MonotherapyExperimentalPatients with solid tumor types considered immunosensitive
  • BAY1905254
Dose escalation_Combination therapyExperimentalPatients with solid tumor types considered immunosensitive
  • BAY1905254 + Pembrolizumab
Expansion Urothelial cancer_MonotherapyExperimentalPatients with urothelial cancer
  • BAY1905254
Expansion Urothelial cancer_Combination therapyExperimentalPatients with urothelial cancer
  • BAY1905254 + Pembrolizumab
Expansion HNSCC_MonotherapyExperimentalPatients with head and neck squamous cell carcinoma (HNSCC)
  • BAY1905254
Expansion HNSCC_Combination therapyExperimentalPatients with head and neck squamous cell carcinoma (HNSCC)
  • BAY1905254 + Pembrolizumab
Expansion Cervical cancer_MonotherapyExperimentalPatients with cervical cancer
  • BAY1905254
Expansion Gastric cancer_Combination therapyExperimentalPatients with gastric/ gastroesophageal junction adenocarcinoma
  • BAY1905254 + Pembrolizumab
Expansion TMB-basket_MonotherapyExperimentalPatients with immunosensitive solid tumor types having a medium-to-high tumor mutational burden (TMB)
  • BAY1905254

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients aged ≥ 18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  Patients with following histologically confirmed, advanced or metastatic solid tumors
             are eligible:

               -  Dose escalation: All solid tumor types with a likelihood of sensitivity to
                  immunotherapy, as judged by the investigator.

               -  TMB-basket expansion cohort of BAY1905254 monotherapy (at MTD or MAD): patients
                  with medium-to-high TMB from selected solid tumor types with a likelihood of
                  sensitivity to immunotherapy

               -  Tumor type-specific high-dose of BAY1905254 monotherapy (at MTD or MAD) expansion
                  cohorts: urothelial cancer, HNSCC and cervical cancer with medium-to-high TMB.
                  The pre-planned tumor types may be changed based on data from the TMB-basket
                  cohort.

               -  Tumor type-specific high-dose of BAY 1905254 in combination with pembrolizumab
                  (at MTD or MAD) expansion cohorts: urothelial cancer, HNSCC and Gastric/
                  Gastroesophageal junction (GEJ) adenocarcinoma.

          -  Provision of archival tumor tissue at screening is mandatory, except for patients in
             the monotherapy TMB-basket expansion cohort.

          -  All dose expansion cohorts: Willingness to undergo paired biopsy of tumor.

          -  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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent AEs (TEAEs) including treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and dose-limiting toxicities (DLTs)
Time Frame:Up to 58 months
Safety Issue:
Description:Maximum plasma concentration after single dose

Secondary Outcome Measures

Measure:Recommended dose of BAY1905254 for Phase 2
Time Frame:Up to 58 months
Safety Issue:
Description:
Measure:Cmax,md after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg
Time Frame:Up to 504 hours after drug in Cycle 3
Safety Issue:
Description:Maximum plasma concentration after multiple doses
Measure:AUC after multiple dosing (Cycle 3) for cohorts receiving doses ≥ 20 mg
Time Frame:Up to 504 hours after drug in Cycle 3
Safety Issue:
Description:Area under the plasma concentration curve after multiple doses
Measure:Incidence of positive anti-drug antibody and neutralizing antibody titer for BAY1905254
Time Frame:Up to 58 months
Safety Issue:
Description:
Measure:Best overall response rate
Time Frame:Up to 58 months
Safety Issue:
Description:Determined by RECIST 1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Neoplasm
  • Immuno oncology drug
  • Urothelial cancer
  • Head and neck squamous cell carcinoma (HNSCC)
  • Cervical cancer
  • Gastric/ Gastroesophageal junction adenocarcinoma

Last Updated

November 25, 2019