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

• ClinicalTrials.gov Identifier: NCT03666273
• Recruitment Status: Recruiting
• First Posted: September 11, 2018
• Last Update Posted: March 29, 2021
• Sponsor: Bayer
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: September 10, 2018
• First Posted Date: September 11, 2018
• Last Update Posted Date: March 29, 2021
• Actual Study Start Date: September 12, 2018
• Estimated Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 19, 2019)

• 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 ]
• Severity 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 ]
• Cmax of BAY1905254 after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg [ Time Frame: Up to 504 hours after drug in Cycle 1 ]
  Maximum plasma concentration after single dose
• AUC of BAY1905254 after first dose administration (Cycle 1) for cohorts receiving doses ≥ 20 mg [ Time Frame: Up to 504 hours after drug in Cycle 1 ]
  Area under the plasma concentration curve after single dose
• Maximum tolerated dose (MTD) of BAY1905254 [ Time Frame: Up to 58 months ]

Original Primary Outcome Measures (submitted: September 10, 2018)

• 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 ]
• 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 ]
• 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
• 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)

Current Secondary Outcome Measures (submitted: November 25, 2019)

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

Original Secondary Outcome Measures (submitted: September 10, 2018)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumor

Intervention

• Drug: BAY1905254
  Intravenous administration of escalating doses of BAY1905254
• Drug: BAY1905254 + Pembrolizumab
  Intravenous administration of BAY1905254 of fixed dose (expansion), and of a fixed dose of pembrolizumab

Study Arms

• Experimental: Dose escalation_Monotherapy
  Patients with solid tumor types considered immunosensitive
  Intervention: Drug: BAY1905254
• Experimental: Dose escalation_Combination therapy
  Patients with solid tumor types considered immunosensitive
  Intervention: Drug: BAY1905254 + Pembrolizumab
• Experimental: Expansion HNSCC_Combination therapy
  Patients with head and neck squamous cell carcinoma (HNSCC)
  Intervention: Drug: BAY1905254 + Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 22, 2020): 120
• Original Estimated Enrollment (submitted: September 10, 2018): 196
• Estimated Study Completion Date: May 30, 2024
• Estimated Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Main Inclusion Criteria:

• Male or female patients aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

• Patients must have measurable disease (at least one unidimensional measurable lesion by Computed tomography [CT] or Magnetic resonance imaging [MRI]) per Response evaluation criteria in solid tumors (RECIST) 1.1, and following histologically confirmed, advanced or metastatic solid tumors:

  • Dose escalation: All solid tumor types with a likelihood of sensitivity to immunotherapy, as judged by the investigator.
  • Expansion of BAY 1905254 in combination with pembrolizumab in Head and neck squamous cell carcinoma (HNSCC): recurrent or metastatic head and neck squamous cell carcinoma IO-naïve PDL1+/ CPS≥1(PD-L1: Programmed death ligand 1; CPS: Combined positive score).
• Provision of archival tumor tissue at screening is mandatory for all patients in dose escalation.
• For dose escalation, 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.

Main 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.
• For dose expansion cohort of BAY 1905254 in combination with pembrolizumab in HNSCC: has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03666273
• Other Study ID Numbers: 18789; MK-3475-920 ( Other Identifier: Merck ); 2018-000990-63 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Merck Sharp & Dohme Corp.

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: March 2021