A Phase I/II clinical study to investigate the safety and effectiveness of BT8009 in patients with advanced malignancies
- Conditions
- ectin-4 Expressing Advanced Malignancies.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002719-23-IT
- Lead Sponsor
- BicycleTx Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 146
1 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.
2 At least 18 years-of-age at the time of signature of the informed consent form.
3 ECOG Performance Status score of 0 or 1.
4Patients must have measurable disease per RECIST v1.1.
5Acceptable organ function, as evidenced by the following laboratory data:
a Renal function, as follows: creatinine clearance of =50 mL/min by the Cockcroft-Gault equation or equivalent.
b Total bilirubin =1.5 × ULN
cSerum albumin =2.5 g/dL
d AST =2.5 × ULN or =5 × ULN in the presence of liver metastases
e ALT =2.5 × ULN or =5 × ULN in the presence of liver metastases
f INR <1.3 or = institutional ULN
6 Acceptable hematologic function:
a Hemoglobin =9 g/dL
b ANC=1500 cells/mm3
c Platelet count =75,000 cells/mm3
7 Negative pregnancy test for WOCBP
8 Availability of archived tumor samples or willingness to provide fresh tumor biopsy during screening.
9 Life expectancy =12 weeks
10 Must be willing and able to comply with the protocol
11 Must have exhausted all standard treatment options
Additional Inclusion Criteria – Part A Only
12 Patients with the following advanced, histologically confirmed malignant solid tumors that recurred after or have been refractory to previous therapy: a) urothelial (transitional cell) carcinoma (fresh biopsy or an archived sample must be submitted); orb) having pancreatic, breast, NSCLC, gastric, esophageal, head and neck, or ovarian tumor tissue (fresh biopsy or an archived sample) testing positive for Nectin-4 expression.
Exceptions: single-subject accelerated cohorts may enroll patients with advanced solid tumors not-restricted to the above definitions, unless the SRC views otherwise. The Sponsor may require a) or b) at any time during the enrollment; eligibility will be confirmed by the Medical Monitor. The Sponsor and/or SRC may decide to require enrollment of specific tumor (sub)types at any point during the escalation to enrich the evaluation of biomarkers, safety, anti-tumor activity, or PK.
Additional Inclusion Criteria – Part B-1 and B-2
13 Patients with solid tumor metastatic recurrent disease confirmed as Nectin-4 positive on fresh biopsy or archived tissue must have failed at least one prior line of therapy with evidence of radiographic progression on the most recent line of therapy. If patient’s tumor has been demonstrated to contain a therapeutically targetable somatic or driver mutation, therapy must be given with appropriate locally-approved therapy, then therapy must have been given based on local standard standards of care. If platinum therapy is applicable, then FDA-approved or appropriate locally-approved therapy must have been given based on local standard guidelines. If prior immunotherapy, the last dose must have been at least 28 days prior to the first dose. The Sponsor and/or SRC may decide to require or limit enrollment of specific tumor (sub)types meeting the above definition at any point during the expansion to enrich the population for anti-tumor activity.
14 At least 6 patients per cohort must have at least 1 tumor lesion amenable to biopsy and must be willing to undergo a biopsy prior to first dose and following any dose in Cycle 1.
Additional Inclusion Criteria – Part C renal insufficiency cohort
15 Patients with solid tumor advanced disease are eligible as follows: 1) 6 patients with a GFR
1. Chemotherapy treatments within 14 days prior to first dose, other anticancer treatments, treatment within 28 days or 5 terminal half-lives, whichever is shorter. Prior toxicities must have resolved to G1 CTCAE v5.0 (except alopecia, which must be no greater than G2).
2. Experimental treatments within 4 weeks of first dose
3. Prior treatment with Nectin-4 targeted therapy
4. Current treatment with strong inhibitors or strong inducers of CYP3A4 or strong inhibitors of P-gp, including herbal- or food-based.
5. Known sensitivity to any of the ingredients of BT8009 or monomethyl auristatin E
6. BSA >2.21 m2
7. Significant condition, including but not limited to eye (dry eye, corneal opacities or keratitis), skin (rash ), life-threatening illness, active uncontrolled infection or organ system dysfunction, or other reasons in the Investigator opinion. Prior = Grade 2 thyroid endocrinopathy is allowed, if appropriately controlled with thyroid hormone and stable for at least 2 months on therapy
8. relevant troponin elevation.
9. Uncontrolled diabetes(HbA1c =8%)
10. Major surgery (excluding placement of vascular access) within 4 weeks and recovered adequately prior to 1st dose
11. Receipt of live or attenuated vaccine within 30 days of 1st dose
12. Uncontrolled, symptomatic brain metastases
13. Patients with uncontrolled hypertension ( Systolic BP =160 mmHg or diastolic BP =100 mmHg) prior to first dose
14. History or current evidence of any condition that might confound the study result, interfere with the patient’s participation, or is not in the best interest of the patient, including but not limited to:
- Patients with history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, congestive heart failure or symptoms of Class III-IV (NYHA)within 6 months prior to first dose or:
a. QT interval (QTcF) >470 msec
b. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
c. Any important abnormalities in rhythm, conduction, or morphology of resting ECGs
15. Known HIV/) AIDS
16. Known HBV and/or anti-HBV core antibody.
17. Active HCV infection with positive viral load if HCV antibody positive (, not applicable if antibody is negative). HCV infected patients can be included if they have sustained virologic response of =12 weeks.
18. History of another malignancy within 3 years before the first dose, or any evidence of residual disease from a previously diagnosed malignancy (excluding adequately treated with curative intent basal cell carcinoma, squamous cell of the skin, cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in situ or ductal carcinoma in situ of the breast)
19. Systemic IV anti-infective treatment, or fever not attributable to underlying malignancy within the last 14 days prior to first dose of BT8009
20. Suspicion of relevant and recent systemic viral syndrome or need for quarantine/isolation that is not resolved in the opinion of the Investigator
21. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol
Additional Exclusion Criteria Part A-2 and B-2 Nivolumab Combination Cohorts
22. Prior intolerance to immune checkpoint inhibitor
23. Known hypersensitivity to checkpoint inhibitor therapy
24. Prior organ transplant (including allogeneic)
25. Diagnosis of clinically relevant immunodeficiency
26. Active system
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