1. Active keratitis or corneal ulcerations.

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.

3. Any condition requiring current treatment with high dose corticosteroids (> 10 mg daily prednisone or equivalent).

4. Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.

5. Has not adequately recovered from recent major surgery (excluding placement of vascular access).

6. Receipt of live or attenuated vaccine within 30 days of first dose.

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.

8. Uncontrolled diabetes, defined as hemoglobin A1C (HbA1c) ≥ 8%.

9. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥ 2 peripheral neuropathy.

10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).

11. Uncontrolled hypertension (HTN) (systolic blood pressure (BP) ≥ 150 mm mercury (Hg) or diastolic BP ≥ 95 mm Hg) prior to first dose.

12. Prior allogeneic stem cell or solid organ transplantation.

13. Active interstitial lung disease or pneumonitis, or a history of interstitial lung disease or pneumonitis requiring treatment with steroids or other immunosuppressive medications.

​

14. Prior treatment with an agent directed to another stimulatory or co-inhibitory T-cell receptor.

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.

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.

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).

18. Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving immune checkpoint inhibitor (CPI).

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.

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.

21. Known active hepatitis C infection with positive viral load if hepatitis C virus (HCV) 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.

22. History or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study.

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.

​

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.

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.

26. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

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.

​

CRITERES D'EXCLUSION COHORTE 1 (NON TRAITE AUPARAVANT) :

28. Prior treatment with a CPI for any other malignancy within the last 12 months.

​

CRITERES D'EXCLUSION COHORTE 2 (TRAITE AUPARAVANT) :

29. Received more than 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen.

30. Prior treatment with enfortumab vedotin or any other MMAE-based therapy

31. Prior participation in any study in which BT8009 was being investigated (including Cohort 1 of this study).

32. Ongoing clinically significant toxicity (Grade ≥ 2) associated with prior treatment for UC (including radiotherapy or surgery).