Bladder - Metastatic

Genitourinary Cancer
Bladder - Metastatic
- 1st Line
  - ALLIANCEUROA031702
    A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
    - Key Eligibilty Criteria:
      Inclusion:
      1. Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
      a. One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
      b. Histologically confirmed diagnosis of one of the following metastatic cohorts:
      - Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
      - Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
      - Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
      - Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation
      - Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
      - Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
      c. H&E slides from diagnostic tumor tissue for retrospective central pathology review
      2. Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
      3. Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed.
      4. No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
      5. The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
  - VICCURO24518
    Phase 1 Study of LOXO-435 (LY3866288) In Adv. Solid Tumors with FGFR3 Alterations Inc. Urothelial
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
      2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
      a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
      b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
      c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
      d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
      3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
      a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
      4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
      
      Exclusion Criteria:
      1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
      2. For Cohort B5 only, individuals with known uncontrolled diabetes.
      3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
      4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.
      
      For pre-screening, please contact: Individual disease research teams.
- 2nd line and Above
  - Prior treatment with PD-1 or PD-L1 in locally advanced or metastatic setting
    - VICCURO24518
      Phase 1 Study of LOXO-435 (LY3866288) In Adv. Solid Tumors with FGFR3 Alterations Inc. Urothelial
      - Key Eligibility Criteria:
        Inclusion Criteria:
        1. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
        2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
        a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
        b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
        c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
        d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
        3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
        a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
        4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
        
        Exclusion Criteria:
        1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
        2. For Cohort B5 only, individuals with known uncontrolled diabetes.
        3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
        4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.
        
        For pre-screening, please contact: Individual disease research teams.
    - VICC-DTPHI23103
      A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults with Select Solid Tumors
      - Key Eligibility Criteria:
        
        Inclusion:
        1. For Phase 1b: locally advanced, recurrent, or metastatic, incurable, and histologically or cytologically confirmed HR+/HER2- breast cancer by ASCO/CAP criteria (based on most recent assessment):
        a) Must have received CDK4/6i in the adjuvant or metastatic setting, unless patient was unable or unwilling to receive standard of care CDK4/6i treatment; or must be able to receive it on protocol, AND,
        b) Received no more than 1 prior line of therapy containing chemotherapy (including cytotoxic antibody-drug conjugates) given in the metastatic setting; AND,
        c) Must have received no more than 3 lines of therapy in total for metastatic disease.
        d) May have received a prior PI3Ka inhibitor
        
        NOTE: If the patient progressed on the PI3K inhibitor a sample (tissue or liquid) must have been obtained following progression, or at study screening, to be analyzed at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory, determine the resistance mutation(s) and Sponsor approval for study inclusion obtained. If the patient was intolerant to the drug, then mutational analysis and Sponsor approval are not required for enrollment.
        
        Exclusion:
        1. Has had tumor evaluated for PTEN and AKT and has known mutations or deletions in PTEN, or, activating mutations in AKT (E17K) determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory (e.g., ISO15189-certified, in-house clinical testing).
        2. Metaplastic breast cancer
        3. Possible allergies to TOS-358 or excipients
        
        For pre-screening, please contact: Message Basket: P VICC RESEARCH BREAST OHO
    - VICC-DTPHI24194
      Phase 1 study of DCC-2812 in Advanced or Metastatic RCC, UC, or CRPC
      - Key Eligibility Criteria:
        Inclusion Criteria:
        1. Must have one of the following diagnoses under study:
        a. RCC: Have histologically or cytologically confirmed advanced or metastatic RCC and have progressed on, are intolerant to, or have a contraindication to treatment with a VEGFR-TKI and an anti-PD-(L)1 antibody.
        b. Urothelial carcinoma: Have histologically or cytologically confirmed advanced or metastatic urothelial carcinoma and have progressed on, are intolerant to, or have a contraindication to treatment with an anti-PD-(L)1 antibody and enfortumab vedotin-ejfv. Participants with susceptible FGFR3 or FGFR2 tumor genetic alterations must have progressed on, be intolerant to, or have a contraindication to treatment with an FGFR inhibitor, if approved and available in the study site's region.
        c. Castration-resistant prostate cancer: Have a histologically or cytologically confirmed advanced or metastatic prostate cancer after treatment with at least 1 androgen receptor signaling inhibitor (such as abiraterone, enzalutamide, apalutamide, and darolutamide). Participants with prostate cancer must also fulfill both of the following:
        i. Ongoing androgen deprivation from prior orchiectomy or continued luteinizing hormone-releasing hormone agonist or antagonist therapy with leuprolide, goserelin, buserelin, triptorelin, or degarelix and a Screening testosterone level of 50 ng/dL or less.
        ii. At least 1 metastatic lesion outside the prostate and at least one of the following: any soft tissue lesion that is measurable according to RECIST v1.1 and/or a PSA level of at least 1 ng/mL.
        
        Exclusion Criteria:
        1. Has history of systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or moderate hemoptysis within 6 months prior to the first dose of study drug.
        2. Has history of systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) unless they have been on stable anticoagulation for at least 30 days or the event has completely resolved and there is no need for ongoing treatment.
        
        For pre-screening, please contact: VICC RESEARCH PHASE 1
  - ALLIANCEUROA031702
    A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)
    - Key Eligibilty Criteria:
      Inclusion:
      1. Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
      a. One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
      b. Histologically confirmed diagnosis of one of the following metastatic cohorts:
      - Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
      - Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
      - Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
      - Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation
      - Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
      - Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
      c. H&E slides from diagnostic tumor tissue for retrospective central pathology review
      2. Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
      3. Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed.
      4. No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
      5. The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
  - VICCURO24518
    Phase 1 Study of LOXO-435 (LY3866288) In Adv. Solid Tumors with FGFR3 Alterations Inc. Urothelial
    - Key Eligibility Criteria:
      Inclusion Criteria:
      1. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
      2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
      a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
      b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
      c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
      d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
      3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
      a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
      4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
      
      Exclusion Criteria:
      1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
      2. For Cohort B5 only, individuals with known uncontrolled diabetes.
      3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
      4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.
      
      For pre-screening, please contact: Individual disease research teams.