ZELENECTIDE PEVEDOTIN for Nectin-4 expressing advanced malignancies

Inclusion criteria

• {"criterion_text":"- 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.\n- 9. Life expectancy ≥12 weeks after the start of zelenectide pevedotin (BT8009) treatment according to the Investigator's judgment.\n- 11. Additional cohort-specific inclusion criteria may apply.\n- 10. 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.\n- 2. At least 18 years-of-age at the time of signature of the informed consent form.\n- 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).\n- 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.\n- 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. (See Cohort specific criteria for Part B-7 and 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.\n- 6. Acceptable hematologic function (no red blood cell or platelet transfusions or growth factors are allowed within 4 weeks of the first dose of zelenectide pevedotin (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.\n- 7. 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 zelenectide pevedotin (BT8009)).\n- 8. Availability of archived tumor samples or willingness to provide fresh tumor biopsy during screening."}

Exclusion criteria

• {"criterion_text":"- 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 zelenectide pevedotin (BT8009). If prior radiation therapy, the last dose must be at least 14 days prior to the first dose of zelenectide pevedotin (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).\n- 10. Major surgery (excluding placement of vascular access) within 4 weeks of first dose of zelenectide pevedotin (BT8009) and must have recovered adequately prior to starting study therapy.\n- 3. Current treatment with strong inhibitors or strong inducers of CYP3A or inhibitors of P-gp including herbal- or food-based.\n- 4. Known hypersensitivity to any of the ingredients of the investigational product(s), including MMAE.\n- 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, including consideration of gastrointestinal, skin and pulmonary co-morbidities and including review of screening chest CT to ensure no clinically significant co-morbidities. Treatment induced ≤ Grade 2 endocrinopathy is allowed, if appropriately controlled with supplemental hormone replacement and stable for at least 2 months on therapy. Skin toxicity should resolve to Grade ≤1.\n- 6. Active keratitis or corneal ulcerations.\n- 7. Grade ≥2 peripheral neuropathy.\n- 8. Clinically relevant troponin elevation (considering local reference standards).\n- 11. Receipt of live or attenuated vaccine within 30 days of study treatment.\n- 9. Uncontrolled diabetes, defined as hemoglobin A1C (HbA1c) ≥8%.\n- 12. Known active or untreated CNS metastases and/or carcinomatous meningitis. (To be eligible, patients with treated brain metastasis may participate in the study if they are stable for at least 4 weeks prior to the first dose, either without the use of steroids or on stable or decreasing dose of less than or equal to 10 mg daily prednisone or equivalent and are without any symptoms that would confound the evaluation of neurologic and other AEs).\n- 18. History or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study.\n- 13. Patients with uncontrolled hypertension (systolic blood pressure [BP] Systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg) prior to first dose of zelenectide pevedotin (BT8009).\n- 14. 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 to participate in the opinion of the Investigator, including but not limited to: a. Patients with history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, congestive heart failure or symptoms of New York Heart Association Class III*-IV documented within 6 months prior to first dose of zelenectide pevedotin (BT8009) or: i. Mean resting corrected QT interval (QTcF) >470 msec. ii. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age. iii. Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third degree heart block.\n- 15. Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (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.\n- 16. Patients with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody and a positive polymerase chain reaction (PCR).\n- 17. Active hepatitis C infection with positive viral load if hepatitis C virus (HCV) 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.\n- 19. Active systemic infection requiring therapy, or fever not attributable to underlying malignancy within the last 14 days prior to first dose of zelenectide pevedotin (BT8009).\n- 2. Experimental treatments within 4 weeks of first dose of zelenectide pevedotin (BT8009).\n- 20. Suspicion of relevant and recent systemic viral syndrome or need for quarantine/isolation that is not resolved in the opinion of the Investigator.\n- 21. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.\n- 22. Prior Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) on any MMAE-conjugated drug.\n- 23. Adults under a legal protection regime: protection of justice, curatorship, guardianship as well as people hospitalized without consent, people deprived of liberty and persons incapable of expressing their consent\n- 24. Additional cohort-specific exclusion criteria may apply."}

Primary endpoints

• {"endpoint_text":"- 1. Incidence of TEAEs, including lab, ECG, vital sign abnormalities (CTCAE v5.0) (A-1,A-2, B-8, B-9, &C).","definition_or_measurement_approach":"Safety assessed as incidence of treatment-emergent adverse events (TEAEs) including laboratory, ECG and vital sign abnormalities graded per CTCAE v5.0 in specified cohorts."}
• {"endpoint_text":"- 2. Incidence of dose-limiting tox (A-1,A-2).","definition_or_measurement_approach":"Dose-limiting toxicities assessed during escalation cohorts (A-1, A-2) using protocol-defined DLT definitions to determine MTD/RP2D."}
• {"endpoint_text":"- 3. ORR per RECIST v1.1 criteria (B).","definition_or_measurement_approach":"Objective response rate measured per RECIST v1.1 by investigator assessment in expansion cohorts (Part B)."}
• {"endpoint_text":"- 4. Plasma concentrations of zelenectide pevedotin (BT8009) and MMAE with derivations including Cmax, Cmin, AUC, and elimination t(1/2) (D).","definition_or_measurement_approach":"Pharmacokinetic measurements of BT8009 and MMAE in plasma with derivations including Cmax, Cmin, AUC and elimination half-life (t1/2) in PK cohorts."}

Secondary endpoints

• {"endpoint_text":"- 1. ORR, DOR, clinical benefit rate (CR + PR + SD ≥ 16 weeks), PFS, all assessed per RECIST v1.1 criteria, and OS (A, C and D).","definition_or_measurement_approach":"Tumor efficacy endpoints including ORR, duration of response (DOR), clinical benefit rate (CR+PR+SD ≥16 weeks), progression-free survival (PFS) per RECIST v1.1, and overall survival (OS) assessed in specified parts/cohorts."}
• {"endpoint_text":"- 2. Plasma concentrations of zelenectide pevedotin (BT8009) and MMAE with derivations including Cmax, Cmin, AUC, and elimination half-life t(1/2) (A, B, C and D).","definition_or_measurement_approach":"PK sampling across cohorts A, B, C and D to derive Cmax, Cmin, AUC and t1/2 for BT8009 and MMAE."}
• {"endpoint_text":"- 3. Measurement of ADA (A, C and D).","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA) in cohorts A, C and D using validated immunogenicity assays."}
• {"endpoint_text":"- 4. TEAEs and laboratory, ECG and vital sign abnormalities using CTCAE v5.0 criteria (B, D).","definition_or_measurement_approach":"Safety monitoring of TEAEs and abnormalities in labs, ECG, and vital signs graded per CTCAE v5.0 in cohorts B and D."}
• {"endpoint_text":"- 5. DOR, clinical benefit rate (CR + PR + SD ≥ 16 weeks), PFS, all assessed per RECIST v1.1 criteria, and OS (B).","definition_or_measurement_approach":"Efficacy endpoints in Part B measured per RECIST v1.1 including DOR, clinical benefit rate, PFS, and OS."}
• {"endpoint_text":"- 6. ORR by Nectin-4 status per RECIST v1.1 criteria (B).","definition_or_measurement_approach":"Objective response rate stratified by tumor Nectin-4 status, assessed per RECIST v1.1 in Part B."}
• {"endpoint_text":"- 7. Plasma concentrations of zelenectide pevedotin (BT8009) and MMAE with derivations including Cmax, Cmin, AUC, and elimination half-life t(1/2) (B).","definition_or_measurement_approach":"PK parameters derived for BT8009 and MMAE in Part B cohorts (Cmax, Cmin, AUC, t1/2)."}
• {"endpoint_text":"- 8. Measurement of ADA (B).","definition_or_measurement_approach":"ADA measurement in Part B using immunogenicity assays."}

Spain

Earliest CTIS Part Ii Submission Date

16-01-2024

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

734

Number Of Sites

6

Number Of Participants

87

France

Earliest CTIS Part Ii Submission Date

16-01-2024

Latest Decision Or Authorization Date

14-01-2026

Processing Time Days

729

Number Of Sites

5

Number Of Participants

124

Italy

Earliest CTIS Part Ii Submission Date

16-01-2024

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

731

Number Of Sites

2

Number Of Participants

43

Primary sponsor

Full Name

Bicycletx Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

code: 8 (pharmacovigilance/safety role indicated by sponsorDuties)

Name

Medpace Inc.

Responsibilities

codes: 1,10,12,13,2,5,6,7,9 (multiple operational responsibilities listed)

Name

4g Clinical LLC

Responsibilities

code: 3

Name

Medpace Inc. (multiple responsibilities)

Responsibilities

central operational/CRO-like functions (codes listed above)

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Tempus Compass LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Imagene AI","duties_or_roles":"code: 15; value: Data analysis","organisation_type":"Industry"}
• {"country":"United States","full_name":"Llx Solutions LLC","duties_or_roles":"code: 15; value: IDMC","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"York Bioanalytical Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Factor","duties_or_roles":"code: 15; value: Legal consult","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Client-Pharma Limited","duties_or_roles":"code: 15; value: Commercial drug sourcing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Lanterne Dx LLC","duties_or_roles":"code: 15; value: FISH slide imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code: 15; value: Central ECG","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"codes: 1,10,12,13,2,5,6,7,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Indica Labs Inc.","duties_or_roles":"code: 15; value: Data analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"York Bioanalytical Solutions Limited (alternate address)","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"DXC (CSC Consulting INC)","duties_or_roles":"code: 15; value: Regulatory publishing","organisation_type":"Health care"}
• {"country":"Spain","full_name":"Ipsory S.L.","duties_or_roles":"code: 15; value: Patient travel reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Matrix Healthcare Solutions Limited","duties_or_roles":"code: 15; value: Commercial drug sourcing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"code: 15; value: Central Imaging Review","organisation_type":"Pharmaceutical company"}