Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients With Advanced Malignancies Associated With EphA2 Expression
This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known for expression of EphA2. The main goals of this study are to: * Find the recommended dose(s) of BT5528 that can be given safely to participants alone and in combination with nivolumab * Learn more about the side effects of BT5528 * Learn about how effective BT5528 is for the treatment of ovarian cancer, urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head and neck cancer (HNSCC), and gastric/upper gastrointestinal cancer. * Learn more about BT5528 therapy alone and in combination with nivolumab.
• Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling or analyses
• At least 18 years-of-age at the time of signature of the informed consent form
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Acceptable renal, hepatic, hematologic and coagulation functions
• Negative pregnancy test for women of childbearing potential
• Male participants with female partners of childbearing potential and female participants of childbearing potential are required to follow highly effective contraception
• All patients must have tumor tissue (fresh or archived) available for analysis of EphA2 tumor expression and other biomarkers. In the absence of available tumor tissue, patients must be willing to undergo a biopsy to provide fresh tumor samples
• Life expectancy ≥12 weeks after the start of BT5528 treatment according to the Investigator's judgment.
• Must be willing and able to comply with the protocol and study procedures.
⁃ Additional inclusion criteria for Phase I (dose escalation phase, with BT5528 alone or in combination with nivolumab):
• Metastatic recurrent histologically confirmed malignant solid tumors historically known for high EphA2 tumor expression. Confirmation of EphA2 expression prior to enrollment is not required for participants with ovarian cancer and specific other individual tumor types.
• Exhausted all appropriate treatment options per local guidelines
• Participants with urothelial cancer who have at least 1 (but no more than 3) prior lines of systemic therapy.
⁃ Additional inclusion criteria for Phase II (dose expansion phase, with BT5528 alone):
• Participants with metastatic recurrent disease histologically confirmed to be non-small cell lung cancer, ovarian cancer, triple-negative breast cancer (TNBC), gastric/upper gastrointestinal (GI) cancer, head and neck (H\&N) cancer, urothelial cancer are eligible and must have failed or are ineligible for all appropriate treatment options per local guidelines and must have evidence of radiographic progression on the most recent line of therapy
• Patients with urothelial cancer who have previously received treatment with enfortumab vedotin (EV) are eligible to the study. Patients who received EV and showed disease progression within 6 months of treatment start are planned for less than 50% of total patients enrolled in the cohort