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