BT8009 for Urothelial cancer | Locally advanced urothelial cancer | Metastatic urothelial cancer

Inclusion criteria

• {"criterion_text":"- 1. Able to understand the study procedures and agree to participate in the study by providing written informed consent.\n- 10. WOCBP and male participants with female partners of childbearing potential willing to follow highly effective contraception at least as conservative as Clinical Trial Facilitation Group (CTFG) recommendations of < 1% failure rate starting at Screening, throughout the study period, and for at least 1 month following the last dose of avelumab, 4 months following the last dose of pembrolizumab, 6.5 months following the last dose of BT8009, and 6 months following the last dose of platinum treatment or gemcitabine, whichever comes last.\n- 11. Fertile male participants must agree to refrain from sperm donation from first dose until at least 1 month following the last dose of avelumab, 4 months following the last dose of pembrolizumab, 6.5 months following the last dose of BT8009, and 6 months following the last dose of platinum treatment or gemcitabine, whichever comes last. Women must not breastfeed or donate eggs from first dose until 1 month following the last dose of avelumab, 4 months following the last dose of pembrolizumab, 6.5 months following the last dose of BT8009, and 6 months following the last dose of platinum treatment or gemcitabine, whichever comes last.\n- Additional cohort specific inclusion criteria may apply (see synopses)\n- 2. ≥ 18 years of age on day of signing informed consent.\n- 3. Histologically or cytologically confirmed locally advanced (unresectable) or metastatic UC of the renal pelvis, ureter, bladder, or urethra. a. Participants with mixed histologies are required to have a dominant transitional cell pattern (≥ 50%).\n- 4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. a. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions post irradiation.\n- 5. Archival or fresh tumor tissue comprising muscle-invasive UC, or locally advanced or metastatic UC should be available for submission to central laboratory.\n- 6. Life expectancy ≥ 12 weeks.\n- 7. Adequate organ function: a. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for participants with Gilbert disease b. Serum albumin ≥ 2.5 g/dL c. Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of liver metastases d. Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of liver metastases e. Alkaline phosphatase ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of liver or bone metastases f. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation adjusted by the patient’s body surface area)\n- 8. International normalized ratio (INR)/prothrombin time (PT) ≤ 1.5 × ULN unless participant is receiving a stable dose of anticoagulant therapy and PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of the appropriate anticoagulants.\n- 9. Negative pregnancy test for women of childbearing potential (WOCBP) (negative serum test at Screening and negative urine or serum test within 72 hours prior to the first dose)."}

Exclusion criteria

• {"criterion_text":"- 1. Active keratitis or corneal ulcerations.\n- 10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).\n- 11. Uncontrolled hypertension (HTN) (systolic blood pressure (BP) ≥ 150 mm mercury (Hg) or diastolic BP ≥ 95 mm Hg) prior to first dose.\n- 12. Prior allogeneic stem cell or solid organ transplantation.\n- 13. Active interstitial lung disease or pneumonitis, or a history of interstitial lung disease or pneumonitis requiring treatment with steroids or other immunosuppressive medications.\n- 14. Prior treatment with an agent directed to another stimulatory or co-inhibitory T-cell receptor.\n- 15. Prior treatment with any systemic anticancer therapy within 2 weeks or 5 half-lives, whichever is longer, prior to initiation of study treatment; the following exceptions are permitted: a. Palliative radiotherapy for UC-related bone or soft tissue metastasis completed > 7 days prior to baseline imaging. b. Androgen deprivation therapy using gonadotropin-releasing hormone (GnRH) agonists. c. Females with hormone receptor-positive breast cancer who are receiving tamoxifen or aromatase inhibitors adjuvant therapy ≥ 3 years.\n- 16. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 2 weeks or 5 half-lives, whichever is longer, prior to first dose of study treatment.\n- 17. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).\n- 18. Any prior Grade ≥ 3 immune-related adverse event while receiving immune checkpoint inhibitor.\n- 19. Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). a. Well controlled HIV will be allowed if the participant meets all the following criteria at inclusion: i. Cluster of differentiation (CD4+) counts ≥ 350 cells/uL; ii. HIV viral load < 400 copies/mL; iii. Without a history of opportunistic infection within the last 12 months; iv. On established antiretroviral therapy (ART) for at least 4 weeks.\n- 2. Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.\n- 20. Known active hepatitis B, defined as positive surface antigen and/or anti-hepatitis B core antibody. Participants with a negative polymerase chain reaction assay are permitted with appropriate antiviral therapy.\n- 21. Known active hepatitis C infection with positive viral load if hepatitis C virus is antibody positive (if antibody is negative then viral load is not applicable). Participants who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of ≥ 12 weeks.\n- 22. History or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study.\n- 24. Suspicion of relevant and recent systemic viral syndrome or need for quarantine/isolation that is not resolved prior to initiation of study treatment in the opinion of the Investigator.\n- 25. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s ability to take part in the full duration of the study, or is not in the best interest of the participant to take part, in the opinion of the Investigator. Participants 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 (NYHA) Class III or IV (Appendix 2) documented within 6 months prior to first dose of study treatment or: a. Mean resting corrected QT interval (QTc) > 470 msec by Fridericia QT correction. b. Any factors that increase the risk of QTc prolongation such as congenital long QT syndrome, or family history of long QT syndrome. c. Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting ECGs, eg, complete left bundle branch block, third degree heart block.\n- 26. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.\n- 27. Prior Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN)/drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), erythema multiforme, symmetric drug-related intertriginous and flexural exanthema (SDRIFE), or Baboon syndrome.\n- 23. Active systemic infection or fever not attributable to underlying malignancy requiring therapeutic oral or IV antibiotics within 14 days prior to start of study treatment. Participants receiving prophylactic antibiotics are eligible.\n- Additional cohort specific exclusion criteria may apply (see synopses)\n- 3. Any condition requiring current treatment with high dose corticosteroids (> 10 mg daily prednisone or equivalent).\n- 4. Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.\n- 5. Has not adequately recovered from recent major surgery (excluding placement of vascular access).\n- 6. Receipt of live or attenuated vaccine within 30 days of first dose.\n- 7. Known active carcinomatous meningitis or untreated central nervous system (CNS) metastases. a. Participants with treated brain metastases 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 ≤ 10 mg daily prednisone or equivalent and are without any symptoms.\n- 8. Uncontrolled diabetes, defined as hemoglobin A1C (HbA1c) ≥ 8%.\n- 9. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥ 2 peripheral neuropathy."}

Primary endpoints

• {"endpoint_text":"- 1. (Cohort 1) PFS, measured by the length of time from date of randomization to date of first documentation of disease progression per RECIST v1.1 assessed by BICR or death (due to any cause), whichever occurs first.","definition_or_measurement_approach":"PFS measured as time from date of randomization to first documentation of disease progression per RECIST v1.1 assessed by blinded independent central review (BICR) or death from any cause."}
• {"endpoint_text":"- 1. (Cohort 2) ORR, measured by the percentage of participants who have achieved either confirmed CR or PR per RECIST v1.1 assessed by BICR.","definition_or_measurement_approach":"ORR measured as percentage of participants with confirmed complete response (CR) or partial response (PR) per RECIST v1.1 assessed by blinded independent central review (BICR)."}

Secondary endpoints

• {"endpoint_text":"- 1. (Cohort 1) ORR, measured by the percentage of participants who have achieved either a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 assessed by BICR. - ORR, measured by the percentage of participants who have achieved either a confirmed CR or PR per RECIST v1.1 assessed by Investigator","definition_or_measurement_approach":"ORR measured as percentage of participants with confirmed CR or PR per RECIST v1.1 assessed by BICR and separately by Investigator assessment."}
• {"endpoint_text":"- 2. (Cohort 1) OS, defined as length of time from date of randomization to date of death from any cause.","definition_or_measurement_approach":"OS measured as time from randomization to death from any cause."}
• {"endpoint_text":"- 3. (Cohort 1) DoR, measured by the time from first documentation of objective response (that is subsequently confirmed) per RECIST v1.1 assessed by - BICR to the first documentation of objective tumor progression (per RECIST v1.1), or to death (due to any cause), whichever occurs first - Investigator to the first documentation of objective tumor progression (per RECIST v1.1), or to death (due to any cause), whichever occurs first","definition_or_measurement_approach":"DoR measured as time from first documentation of objective response (subsequently confirmed) per RECIST v1.1 to first documentation of objective tumor progression per RECIST v1.1, or death; assessed by BICR and by Investigator."}
• {"endpoint_text":"- 1. (Cohort 2) DoR, measured by the time from first documentation of objective response (that is subsequently confirmed) per RECIST v1.1 assessed by BICR to the first documentation of objective tumor progression (per RECIST v1.1), or to death (due to any cause), whichever occurs first.","definition_or_measurement_approach":"DoR measured as time from first documentation of objective response (confirmed) per RECIST v1.1 assessed by BICR to first documentation of objective tumor progression per RECIST v1.1, or death."}
• {"endpoint_text":"- 2. (Cohort 2) ORR, measured by the percentage of participants who have achieved either confirmed CR or PR per RECIST v1.1 assessed by the Investigator.","definition_or_measurement_approach":"ORR measured as percentage of participants with confirmed CR or PR per RECIST v1.1 assessed by Investigator."}
• {"endpoint_text":"- 3. (Cohort 2) DoR, measured by the time from first documentation of objective response (that is subsequently confirmed) per RECIST v1.1 assessed by Investigator to the first documentation of objective tumor progression (per RECIST v1.1), or to death (due to any cause), whichever occurs first.","definition_or_measurement_approach":"DoR measured as time from first documentation of objective response (confirmed) per RECIST v1.1 assessed by Investigator to first documentation of objective tumor progression per RECIST v1.1, or death."}

Spain

Earliest CTIS Part Ii Submission Date

14-02-2024

Latest Decision Or Authorization Date

16-04-2024

Processing Time Days

62

Number Of Sites

13

Number Of Participants

48

Primary sponsor

Full Name

Bicycletx Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Medpace Inc.

Responsibilities

sponsorDuties codes: ["1","10","12","15","2","5","6","7","9"]; contact email: RS-Advisor-Support@Medpace.com

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: ["8"]; contact email: MHGSafety@iconplc.com

Name

Almac Clinical Services Limited

Responsibilities

sponsorDuties codes: ["14"]; contact email: acsregulatorycompliance@almacgroup.com

Name

QPS Netherlands B.V.

Responsibilities

sponsorDuties codes: ["4"]; contact email: info@qps.com

Third parties

• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: Pharma_Project_Support_Team@neogenomics.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Novasco","duties_or_roles":"sponsorDuties codes: [\"15\"] value: Patient travel reimbursement, contact email: nateo@novasco.fr","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"sponsorDuties codes: [\"15\"] value: Patient travel reimbursement, contact email: administracion@bonotaxi.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"York Bioanalytical Solutions Limited","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: fern.adams-dam@yorkbio.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [\"14\"], contact email: acsregulatorycompliance@almacgroup.com","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: info@qps.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Factor","duties_or_roles":"sponsorDuties codes: [\"15\"] value: Legal Consultant","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"sponsorDuties codes: [\"1\",\"10\",\"12\",\"15\",\"2\",\"5\",\"6\",\"7\",\"9\"] value (one): Patient travel reimbursement; contact email: RS-Advisor-Support@Medpace.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: mrl-be-pm@medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: MRL-US-PM@Medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties codes: [\"3\"], contact email: info@4gclinical.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [\"8\"], contact email: MHGSafety@iconplc.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biotel Research LLC","duties_or_roles":"sponsorDuties codes: [\"15\"] value: Central Imaging Review, contact email: Johnda.Snyder@iconplc.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC (second entry)","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: MRL-US-PM@Medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc. (listed in third parties)","duties_or_roles":"sponsorDuties codes: [\"4\"], contact email: Pharma_Project_Support_Team@neogenomics.com","organisation_type":"Laboratory/Research/Testing facility"}