Rimegepant Plus Toripalimab in Advanced Urothelial Carcinoma After Failure of Standard Therapy

Prior treatment

• Prior allogeneic stem-cell or solid-organ transplantation.
• Current or prior congenital or acquired immunodeficiency disorder.
• Known or suspected allergy to an anti-programmed cell death protein 1 (anti-PD-1) agent, history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergy to any excipient of either investigational product.

Other illness

• History of a malignancy other than urothelial carcinoma, except in either of the following circumstances:
  • The prior malignancy was treated with potentially curative therapy and there has been no evidence of disease for 5 years.
  • Successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or another carcinoma in situ.
• An active or poorly controlled serious infection, including any of the following:
  • Positive for antibodies to human immunodeficiency virus type 1 or 2 (HIV-1/2).
  • Active hepatitis B, defined as hepatitis B surface antigen (HBsAg) positivity or hepatitis B virus (HBV) DNA \>2,000 IU/mL accompanied by abnormal liver function.
  • Active hepatitis C, defined as hepatitis C virus (HCV) antibody positivity or HCV RNA ≥10³ copies/mL accompanied by abnormal liver function.
  • Active tuberculosis.
  • Any other uncontrolled active infection of Grade 3 or higher according to NCI CTCAE v6.0.
• Failure to recover from surgery, such as the presence of an unhealed incision or serious postoperative complications.

Lab values

• Other clinically significant abnormalities in clinical status or laboratory test results that, in the investigator's opinion, may affect the safety assessment, such as uncontrolled diabetes mellitus, chronic kidney disease, Grade 2 or higher peripheral neuropathy according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0 (NCI CTCAE v6.0), or thyroid dysfunction.

Other

• Participants who are pregnant or breastfeeding, or female or male participants of reproductive potential who are unwilling or unable to use effective contraception.
• Any other circumstance that the investigator considers unsuitable for enrollment.

• The participant voluntarily agrees to participate in this study, provides written informed consent, and is willing and able to comply with all study visits and the treatment plan.
• Male or female participants aged ≥18 years.
• Histologic or cytologic confirmation of locally advanced or metastatic urothelial carcinoma.
• The participant's most recent standard therapy must have failed, and disease progression during or after treatment must be radiographically confirmed.
  • Standard therapies include, but are not limited to, platinum-containing chemotherapy regimens; programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor monotherapy; or a PD-1/PD-L1 inhibitor in combination with chemotherapy or an antibody-drug conjugate (ADC).
  • Participants previously treated with a PD-1/PD-L1 inhibitor may be enrolled, except those who permanently discontinued such treatment because of an immune-related adverse event.
• At least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• The most recent adequate archival tumor tissue specimen obtained within the previous 12 months must be provided as a formalin-fixed, paraffin-embedded block or serial unstained sections. Fresh tumor biopsies at baseline and at disease progression for exploratory biomarker research are strongly recommended but not required; a participant's decision whether to undergo biopsy will not affect eligibility for the main part of this clinical trial.
• Estimated life expectancy of at least 6 months.
• Eastern Cooperative Oncology Group (ECOG) score (PS) of 0 or 1.
• Adequate major-organ function.