Bladder Cancer Research & Trials

Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Bacillus Calmette-Guerin (BCG) in Participants with High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) that is Persistent or Recurrent Following BCG Induction

Inclusion Criteria:

• Histologically confirmed by BICR diagnosis of non-muscle invasive (T1, high-grade Ta and/or CIS) TCC of the bladder

• Have been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC defined as at least 5 intravesical instillations of BCG within a 10-week period of time; if more than one induction course or any maintenance therapy of BCG has been received, the participant is not eligible for this study

• Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC defined as:
  – HR NMIBC: Recurrent T1, high-grade Ta and/or CIS
  – Persistent: Remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction (Note: persistent T1 not eligible for study), or
  – Recurrent: Reappearance of high-risk NMIBC after achieving a CR or tumor- free state within 6 months (+ 4 weeks) after start of BCG induction. The recurrence must be within 24 months of last exposure to BCG [with up to an additional 56 days allowed to account for delays in the 24-month assessment].

Exclusion Criteria:

• Has persistent (remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction) T1 disease following an induction course of BCG

• Has muscle invasive (i.e., T2, T3, T4), locally advanced non-resectable or metastatic urothelial carcinoma

• Note: BICR confirmation of the absence of locally advanced or metastatic disease is required prior to participant randomization

• Has concurrent extra-vesical (i.e., urethra, ureter, renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium, concurrent upper tract involvement, or invasive prostatic TCC including T1 or greater disease, or ductal invasion

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).

Note: Participants with biopsy proven low-grade disease or CIS of the prostate are eligible.

Principal Investigator:

Kenneth Ogan, MD

Co-Investigators & Collaborators:

Bradley Carthon, MD (Department of Hematology and Medical Oncology); Viraj Master, MD, PhD; Mehmet Bilen, MD (Department of Hematology and Medical Oncology)

Randomized Phase 2 Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Subjects Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) and FGFR Mutations or Fusions

Inclusion Criteria:

• Histologically confirmed, recurrent, non-muscle-invasive UCC (any variant) of the bladder

• Positive FGFR mutations or fusions as determined by local or central testing at the time of recurrence after BCG therapy: FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2 and FGFR3 gene fusions (FGFR2-BICC1, FGFR2-CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1)

• BCG-unresponsive subjects must meet at least one of the following:
  – Persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy (Cohort 2 only)
  – Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy
  – T1 high-grade at the first disease assessment following an induction BCG course

• BCG experienced subjects must meet the following:
  – Recurrent high-grade Ta/T1 disease within 12 months of completion of BCG therapy (At least 5 of 6 full doses of an initial induction course OR at least 5 of 6 full doses of an initial induction course plus at least 1 maintenance (2 of 3 weekly doses) in a 6-month period) 

• Cohort 1: may be BCG-unresponsive or BCG experienced

• Cohort 2: must be BCG-unresponsive                                                       

Exclusion Criteria:

• Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder

• Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder

• Prior treatment with an FGFR inhibitor

• Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study (UTUC is included in this)

Principal Investigator: 

Viraj Master, MD, PhD

Co-Investigators & Collaborators: 

Kenneth Ogan, MD; Shreyas Joshi, MD, MPH; Aaron Lay, MD; Mehmet Bilen, MD (Department of Hematology and Medical Oncology); Bradley Carthon, MD (Department of Hematology and Medical Oncology)

Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects with Invasive Urothelial Carcinoma with Susceptible FGFR3 Genetic Alterations (PROOF 302)

Inclusion Criteria:

• Histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal ureterectomy, or cystectomy

• If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be AJCC Stage ≥ ypT2 and/or yN+

• If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky, et al. (2011):
  – Creatinine clearance ≤60 mL/min, or
  – CTCAE Grade ≥2 hearing loss, or
  – CTCAE Grade ≥2 neuropathy

• If cisplatin ineligible, must meet the following criteria:
  – Upper tract disease should be AJCC Stage ≥pT2 pN0-2 M0
  – UBC should be AJCC Stage ≥pT3 or pN+

• Must have a centrally reviewed negative postoperative CT or negative biopsy within 28 days before randomization to confirm absence of disease at baseline

• ECOG performance status of ≤2

Exclusion Criteria:

• Presence of positive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy

• Have received BCG or other intravesical therapy for NMIBC within previous 30 days

• Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4, and medications which increase serum phosphorus and/or calcium concentration

• Have a history of primary malignancy within the past 3 years

• Have current evidence of corneal or retinal disorder/keratopathy

• Have a history and/or current evidence of extensive tissue calcification

• Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib

• Have amylase or lipase >2.0 × ULN

• Have insufficient hepatic and renal function

• Have any other concurrent disease or condition that, in the view of the investigator, would interfere with study participation

Principal Investigator: 

Viraj Master, MD, PhD

Co-Investigators & Collaborators: 

Mehmet Bilen, MD (Department of Hematology and Medical Oncology); Bradley Carthon, MD (Department of Hematology and Medical Oncology); Kenneth Ogan, MD; Shreyas Joshi, MD, MPH; Aaron Lay, MD

Phase 3 Study of CG0070 in Patients with Non-Muscular Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus-Calmette-Guerin (BCG)

Inclusion Criteria:

• BCG-unresponsive, high-risk NMIBC (CIS, T1, or high-grade Ta)

• At least 1x iBCG + 1x mBCG

• Histology that is >50% TCC

• Medically unfit or refused cystectomy

• BCG unresponsive NMIBC requires the following to qualify for the study:
  – Relapsed or persistent HGUC (e.g., CIS with or without high-grade Ta or T1 disease) within 12 months of completion (last dose) of adequate BCG treatment
  – Complete qualifying BCG treatment (e.g., “5+2”) within 12 months of the initial qualifying dose of BCG
  – Induction & maintenance must be completed over no more than a 12-month period

• Prior adequate BCG therapy defined as:
  – At least 5 of 6 doses of an initial induction course + at least 2 of 3 doses of maintenance therapy, OR
  – At least 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second induction course

• "5+2" minimum BCG must be completed within 12 months of the initial qualifying BCG induction dose

Exclusion Criteria:

• Current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer

• UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) or prostatic urethra (including CIS of the urethra) within 24 months of enrollment

• Received systemic anti-cancer therapy, including investigational agents 4 weeks before day 1 of Tx 

• Prior systemic treatment, radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies

• Within 6 months prior to starting study treatment, has experienced: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure

• Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies as per standard of care

• Has an active infection requiring systemic therapy

• History of other malignancy within 3 years except low risk prostate cancer

• IVE therapy within 8 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted up to 14 to 60 days prior to beginning study treatment

Principal Investigator:

Shreyas Joshi, MD, MPH