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
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.
18 Years and up
Accepting Healthy Volunteers?
- 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.
- 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.
- Solid Tumors