Nectin-4 Expressing Advanced Malignancies. MedDRA version: 21.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: BT8009
Product Code: BT8009
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: BT8009
Current Sponsor code: BT8009
Other descriptive name: BCY8245
Concentra
Sponsors
BicycleTx Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years old at the time informed consent is given. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 3. Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 4. Acceptable organ function, as evidenced by the following laboratory data: a) Renal function: creatinine clearance of =50 mL/min by the Cockcroft-Gault equation or equivalent. b) Total bilirubin =1.5 × ULN (upper limit of normal) c) Serum albumin =2.5 g/dL d) Aspartate aminotransferase (AST) =2.5 × ULN or =5 × ULN in the presence of liver metastases e) Alanine aminotransferase (ALT) =2.5 × ULN or =5 × ULN in the presence of liver metastases f) International normal ratio (INR) <1.3 or = institutional ULN 5. Acceptable hematologic function (no red blood cell or platelet transfusions or growth factors are allowed within 4 weeks of the first dose of BT8009): a) Hemoglobin =9 g/dL b) Absolute neutrophil count (ANC) =1500 cells/mm³ c) Platelet count =75,000 cells/mm³ 6. Negative pregnancy test for women of childbearing potential (WOCBP) (negative serum test at screening and negative urine or serum test within 3 days prior to the first dose of BT8009. Male patients with female partners of childbearing potential and female patients of childbearing potential are required to follow highly effective contraception (oral and hormonal contraceptives allowed) at least as conservative as Clinical Trial Facilitation Group (CTFG) recommendations for less than 1% failure rate during their participation in the study and for 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 6 months following last dose of study drug and women must not breastfeed during that time or donate eggs. 7. Availability of archived tumor samples within 12 months prior to the date of the first dose of BT8009 or willingness to provide fresh tumor biopsy during screening. 8. Life expectancy =12 weeks after the start of BT8009 treatment according to Investigator's judgment. Additional Inclusion Criteria for Part A 9. Patients with advanced, histologically confirmed malignant solid tumors as follows: a) urothelial (transitional cell) carcinoma naïve to Nectin-4 directed therapies; or b) having tumor tissue (fresh biopsy or on archived sample less than 12 months old without intervening anti-cancer therapies) testing positive for Nectin-4 expression; or c) solid tumors known to be historically associated with Nectin-4 as follows: pancreatic, TNBC, NSCLC, gastric, esophageal or ovarian. Exceptions: single-subject accelerated cohorts may enroll patients with advanced solid tumors non-restricted to the above definitions, unless the Safety Review Committee views otherwise. All patients must have disease that recurred after or refractory to previous therapy including appropriate targeted therapies, for example EGFR or ALK therapies for relevant oncogene driver NSCLC patients, and are candidates for a Phase I study due to lack of approved or standard options for treatment. Additional Inclusion Criteria for Parts B-1 and B-2 Nectin-4 basket monotherapy and combination cohorts 10. Patients with solid tumor metastatic recurrent disease confirmed to express Nectin-4 on fresh biopsy or archived tissue (<12 months old and with no intervening anti-cancer therapies) are eligible and must have exhausted all standard treatment options, including
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded: 1. Chemotherapy treatments within 14 days prior to first dose of study treatment. 2. Other anticancer treatments within 28 days or 5 half-lives, whichever is shorter. Prior toxicities must have resolved to Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 (except alopecia which must be no greater than Grade 2). 3. Experimental treatments within 4 weeks of first dose of BT8009. 4. Prior treatment with Nectin-4 targeted therapy. 5. Current treatment with strong inhibitors or strong inducers of CYP3A4 or strong inhibitors of P-gp including herbal or food based. 6. Known sensitivity to any of the ingredients of the investigational product or monomethyl auristatin E (MMAE). 7. Weight >100 kg or BSA >2.21 m² (representing human 100 kg equivalent for height of 175 cm). 8. Conditions related to or that may confound monitoring for dry eye, corneal opacities or keratitis); skin conditions related to or that may confound monitoring for rash, life-threatening illness, active uncontrolled infection or organ system dysfunction, or other reasons which in the Investigator opinion could compromise the patient’s safety, or interfere with or compromise the integrity of the study. 9. Clinically relevant troponin elevation 10. Uncontrolled diabetes defined as HbA1c =8% 11. Major surgery <4 weeks of first dose of BT8009 12. Receipt of live vaccine <30 days of study treatment 13. Uncontrolled, symptomatic brain metastases 14. Patients with uncontrolled hypertension (systolic BP =160 mm Hg or diastolic BP =100 mm Hg) prior to first dose of BT8009 15. History or current evidence of 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. 16. HIV or acquired immune deficiency syndrome (AIDS) 17. Patients with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody. Patients with a negative polymerase chain reaction (PCR) assay are permitted with appropriate antiviral therapy 18. Active hepatitis C infection with positive viral load. Patients who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of =12 weeks. 19. History of another malignancy within 3 years before the first dose of BT8009, or any evidence of residual disease from a previously diagnosed malignancy 20. Systemic IV anti-infective treatment, or fever within 14 days prior to first dose of BT8009 21. Suspicion of relevant and recent systemic viral syndrome or need for quarantine/isolation that is not resolved in the opinion of the investigator 22. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures Additional Exclusion Criteria for Part A-2 and B-2 Nivolumab Combination Cohorts 23. Prior intolerance to immune checkpoint inhibitor 24. Known hypersensitivity to checkpoint inhibitor therapy 25. Prior organ transplant (including allogeneic) 27. Diagnosis of clinically relevant immunodeficiency 28. Active systemic infection requiring therapy 29. More than 10 mg daily prednisone equivalent or other strong immunosuppressant 30. History of autoimmune disease except type I DM well contained on insulin, alopecia or vitiligo 31. History of interstitial lung disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The clinical study will investigate BT8009 given alone and given in combination with Opdivo (nivolumab). The primary objectives are: 1. To assess the safety and tolerability of BT8009 given alone to patients with advanced solid tumor malignancies or given in combination with Opdivo. 2. To define the maximum tolerated dose (MTD) of BT8009 given alone and in combination with Opdivo, and to determine a recommended dose for the next phase of clinical studies. 3. Assess the clinical activity of BT8009 in patients with solid tumor associated with Nectin-4 expression as a monotherapy and in combination with nivolumab. ;Secondary Objective: The secondary objectives of the clinical study are: 1. To assess preliminary signals of anti-tumor activity achieved with BT8009 administration in patients with advanced solid tumor malignancies as a monotherapy and in combination with nivolumab. 2. To determine the maximum concentration of BT8009 (given alone and in combination with Opdivo) in blood and the rate at which the drug is metabolized. The sponsor will also assess the incidence of development of antibodies to BT8009. 3. To assess safety and tolerability of BT8009 in patients with advanced solid tumor malignancies when given alone and in combination with Opdivo. ;Primary end point(s): The primary outcome measures for Parts A and C will be: 1) The incidence of treatment-emergent adverse events (TEAEs), including laboratory, ECG, and vital sign abnormalities. 2) The incidence of dose-limiting toxicites. The primary outcome measures for Part B will be: 1) Objective response rate (ORR) 2) Duration of response (DOR) 3) Clinical benefit rate (CR + PR + SD = 6 weeks) 4) Time to tumor progression (TTP) 5) Progression-free survival time (PFS) 6) Rate of PFS at 6 months 7) Rate of Overall Survival (OS) at 12 months all assessed per RECIST v1.1 criteria ;Timepoint(s) of evaluation of this end point: Primary outcome measures will be assessed at pre-s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcome measures for Parts A and C will be: 1) Objective response rate (ORR) 2) Duration of response (DOR) 3) Clinical benefit rate (CR + PR + SD = 6 weeks) 4) Time to tumor progression (TTP) 5) Progression-free survival time (PFS) 6) Rate of PFS at 6 months 7) Rate of Overall Survival (OS) at 12 months all assessed per RECIST v1.1 criteria The primary outcome measures for Part B will be: 1) The incidence of treatment-emergent adverse events (TEAEs), including laboratory, ECG, and vital sign abnormalities. Secondary endpoints applicable to all parts of the study include: 1) Plasma concentrations of BT8009 with derivations including Cmax, Cmin, AUC, and elimination half-life t(1/2). ;Timepoint(s) of evaluation of this end point: Secondary outcome measures will be assessed at pre-specified time points throughout the duration of the study (approximately 3 years) | — |
Countries
Belgium, Canada, France, Germany, Hong Kong, Italy, Korea, Republic of, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactDebra Haynes
Sarah Cannon Development Innovations, LLC
Outcome results
None listed