Study BT8009-100 in Patients with Nectin-4 Expressing Advanced Malignancies.

Phase 1

Recruiting

• Conditions: ectin-4 Expressing Advanced Malignancies.; MedDRA version: 20.0Level: SOCClassification code: 10029104Term: Neoplasms benign malignant and unspecified (incl cysts and polyps) Class: 2; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-509781-37-00
• Lead Sponsor: Bicycletx Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-27
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

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., 10. Additional cohort-specific inclusion criteria may apply., 2. At least 18 years-of-age at the time of signature of the informed consent form., 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. Patients who are in Cohort B-7 (cisplatin-ineligible urothelial cancer) can have an ECOG of 2 but must meet additional criteria (see Incl #29)., 4. Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (see Appendix B). Target lesions that were previously irradiated may be measurable if demonstrated progression has occurred., 5. Acceptable organ function, as evidenced by the following lab data: a) Renal function, as follows: creatinine clearance (CrCl) of =50 mL/min by the Cockcroft-Gault equation or equivalent. (Except for patients in the renal impairment cohort [Part C]). b) Total bilirubin =1.5 × upper limit of normal (ULN) or =3 × ULN and conjugated bilirubin =1.5 × ULN for patients with Gilbert syndrome. 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) =1.5 or = institutional ULN unless patient is receiving a stable dose of anticoagulant therapy and PT or aPPT is within therapeutic range of intended use of anticoagulants. g) Acceptable hematologic function (no red blood cell or platelet transfusions or growth factors are allowed within 4 weeks of the first dose of BT8009); except for patients in the renal impairment cohorts; [Part C]: 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)., 7. Availability of archived tumor samples or willingness to provide fresh tumor biopsy during screening., 8. Life expectancy =12 weeks after the start of BT8009 treatment according to the Investigator's judgment., 9. Must be willing and able to comply with the protocol, the scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.

Exclusion Criteria

1. Chemotherapy treatments within 14 days prior to first dose of study treatment. For other anticancer treatments, treatment within 28 days or 5 terminal half-lives, whichever is shorter. If prior immunotherapy, the last dose must be at least 28 days prior to the first dose of BT8009. If prior radiation therapy, the last dose must be at least 14 days prior to the first dose of BT8009. 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)., 18. History or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study., 19. Active systemic infection requiring therapy, or fever not attributable to underlying malignancy within the last 14 days prior to first dose of BT8009., 2. Experimental treatments within 4 weeks of 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., 22. Prior Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) on any MMAE-conjugated drug., 23. Prior intolerance or known hypersensitivity to immune checkpoint inhibitor., 24. Received any prior treatment with stimulatory or co- inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonist or CTLA-4 inhibitors a. Prior treatment with a PD-1, PD-L1 or PD-L2 inhibitor is permitted., 25. Prior organ transplant (including allogeneic)., 26. Diagnosis of clinically relevant immunodeficiency., 10. Major surgery (excluding placement of vascular access) within 4 weeks of first dose of BT8009 and must have recovered adequately prior to starting study therapy., 27. Any condition requiring treatment with >10 mg daily prednisone equivalent or other strong immunosuppressant., 28. Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g. with the use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systematic treatment. Patients with type 1 DM well controlled on insulin, alopecia, or vitiligo are not excluded per this criteria., 3. Current treatment with strong inhibitors or strong inducers of CYP3A or inhibitors of P-gp including herbal- or food-based., 29. Active interstitial lung disease or pneumonitis, or a history of interstitial lung disease or pneumonitis requiring treatment with steroids or other immunosuppressive medications., 30. Additional cohort-specific exclusion criteria may apply., 4. Known hypersensitivity to any of the ingredients of the investigational product(s), including MMAE., 5. Significant medical condition including but not limited to skin (conditions related to or that may confound monitoring for rash including but not limited to autoimmune conditions such as eczema or psoriasis), life-threatening illness, active uncontrolled infection or organ system dysfunction (such as ascites, coagulopathy, encephalopathy), or other reasons which, in the Investigator opinion, could compromise the patient’s safety, or interfere with or compromise the integrity of the study outcomes

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified