Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients with Advanced Malignancies Associated with EphA2 Expressio
- Conditions
- Advanced Malignancies Associated with EphA2 ExpressionMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003653-29-BE
- Lead Sponsor
- BicycleTx Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 288
1. Written informed consent; at least 18 years of age
2. ECOG Performance Status score of 0 or 1; measurable disease per RECIST v1.1
3. Acceptable organ function:
- Creatinine clearance =50 mL/min by Cockcroft-Gault equation or 24-hour urine collection
- Total bilirubin =1.5 × ULN
- Serum albumin =2.5 g/dL
- AST =2.5 × ULN or =5 × ULN in presence of liver metastases
- ALT =2.5 × ULN or =5 × ULN in presence of liver metastases
- INR <1.3 or = institutional ULN
4. Acceptable hematologic function (no red blood cell or platelet transfusions or growth factors allowed within 4 weeks of first dose of BT5528):
- Hemoglobin =9 g/dL
- ANC =1500 cells/mm3
- Platelet count =75,000 cells/mm3
5. Negative pregnancy test for women of childbearing potential. Male patients with female partners of childbearing potential and female patients of childbearing potential must follow highly effective contraception (oral and hormonal contraceptives allowed) at least as conservative as Clinical Trial Facilitation Group recommendations for less than 1% failure rate during participation in the study and for 6 months after last dose of study drug. Male patients must refrain from donating sperm during study participation and for 6 months after last dose of study drug and women must not breastfeed or donate eggs.
6. 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.
7. Life expectancy =12 weeks 10. Willing and able to comply with protocol and study procedures.
Additional Inclusion Criteria – Part A
1. Patients with metastatic recurrent histologically confirmed malignant solid tumor who must have exhausted all appropriate treatment options per local guidelines and must have failed at least one prior line of therapy with evidence of radiographic progression on the most recent line of therapy. If applicable, for patients who received prior immunotherapy, the last dose must have been at least 28 days prior to the first dose of BT5528 study treatment. Patients with pancreatic cancer are allowable but are planned for less than 50% of total patients enrolled in each escalation cohort. The Sponsor or SRC may decide to require enrollment of specific tumor types or subtypes at any point during the escalation if it is felt necessary to enrich the evaluation of biomarkers, safety or PK in a specific tumor type.
2.Patients enrolling in Cohort A1-4 or later for the Part A-1 monotherapy, or enrolling in Cohort A2-3 or later for the Part A-2 combination therapy, must have tumor tissue (fresh or archived) submitted to central laboratory with confirmation of positive EphA2 tumor expression prior to initiating study treatment. Patients with Ovarian or urothelial cancer enrolling in Cohort A1-4 or later for the Part A-1 monotherapy, or enrolling in Cohort A2-3 or later for the Part A-2 combination therapy must have tumor tissue (fresh or archived) available for central laboratory for retrospective analysis of EphA2 tumor expression but may be enrolled without prior confirmation of EphA2 expression.
Additional Inclusion Criteria – Part B
1. Patients with metastatic recurrent disease histologically confirmed to be non-small cell lung cancer (NSCLC), ovarian cancer, triple-negative breast cancer (TNBC), gastric/upper gastrointestinal (GI) cancer, head and neck (H&N) cancer, or urothelia
1. Chemotherapy treatments within 14 days prior to first dose of study treatment. For other anticancer treatments, treatment within 28 days or 5 half-lives, whichever is shorter. For immunotherapy, including immune checkpoint inhibitors, treatment within 28 days prior to the first dose of study treatment.
2. Experimental treatments within 4 weeks of first dose of BT5528 study treatment.
3. 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).
4. Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors of P-gp including herbal- or food-based.
5. Known sensitivity to any of the ingredients of investigational product or MMAE.
6. Significant medical condition, life-threatening illness, active uncontrolled infection or organ system dysfunction (such as ascites, coagulopathy, encephalopathy), or other reasons which could compromise patient’s safety, or interfere with or compromise study outcome integrity including consideration of gastrointestinal, skin and pulmonary co-morbidities and including review of screening chest CT to ensure no clinically significant co-morbidities.
7. Major surgery (excluding placement of vascular access) within 4 weeks of first dose of BT5528 study treatment and must have recovered adequately prior to starting study therapy
8. Receipt of live vaccine within 30 days of study treatment
9. Untreated CNS metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
a. CNS metastases have been clinically stable for at least 6 weeks prior to screening
b. If requiring steroid treatment for CNS metastases, the subject is on a stable or decreasing dose of =20 mg/day of prednisone or equivalent for at least 2 weeks
c. Baseline scans show no evidence of new or enlarged brain metastasis
d. Subject does not have leptomeningeal disease
e. Subject must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
10. Uncontrolled hypertension (systolic BP =160 mmHg; diastolic BP =100 mmHg that is responsive to intervention) at screening or prior to initiation of study drug.
11. History or current evidence of any condition, therapy or laboratory abnormality that might confound study results , interfere with patient’s participation, or is not in the best interest of the patient to participate
12. Known HIV or AIDS
Note: Well controlled HIV will be allowed if the patient meets all the following criteria at inclusion:
a) CD4+ T-cell (CD4+) counts =350 cells/uL;
b) HIV viral load <400 copies/mL
c) Without a history of opportunistic infection within the last 12 months.
d) On established antiretroviral therapy (ART) for at least 4 weeks. Use of anti-retroviral therapy is permitted, but should be discussed with the Medical Monitor on a case-by-case basis.
13. Patients with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody. Patients with a negative PCR assay are permitted with appropriate antiviral therapy
14. Active hepatitis C infection with positive viral load if hepatitis C virus antibody positive (if antibody is negative then viral load not applicable). Patients who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of =12 weeks.
15. Thromboembolic events and/or bleeding disorders within 3 months (e.g., deep vein thrombosis or pulmonary e
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method