Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients with Advanced Malignancies Associated with EphA2 Expression
Details
Brief Summary:
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 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.
Eligibility
You can join if...
Please note this may not be a complete list of eligibility criteria. We have included a few examples of study criteria to help you better understand how your eligibility in the study will be determined; your study team will go through the study eligibility criteria with you to verify if you qualify for participation in this study.
Inclusion Requirements
You can participate in this study if you
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 greater than 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
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
Exclusion Requirements
You cannot participate in this study if you
Chemotherapy treatments within 14 days prior to first dose of study treatment, other anticancer treatments, treatment within 28 days or 5 half-lives, whichever is the shorter
Experimental treatments within 4 weeks of first dose of BT5528
Prior toxicities must have resolved to Grade 1 per Common Terminology Criteria for Adverse - - Events (CTCAE) v 5.0 (except alopecia which can be Grade 2)
Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors of P-gp
Known sensitivity to any of the ingredients of the investigational product or monomethyl auristatin E (MMAE)
Any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with the patient's participation, or is not in the best interest of the patient to participate in the opinion of the investigator including but not limited to specific cardiovascular criteria
Major surgery (excluding placement of vascular access) within 4 weeks of first dose of BT5528 study