A Phase 1B Study of B-701 in Combination With Pembrolizumab in Relapsed or Refractory Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract
A Phase 1B Study of B-701 in Combination With Pembrolizumab in Relapsed or Refractory Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract
This research study is studying a combination of two experimental drugs as a possible treatment for Bladder Cancer that recurred after treatment with standard therapy, or Bladder Cancer that got worse while on treatment with standard therapy.
The following interventions will be involved in this study:
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved B-701 as a treatment for any disease.
The FDA has not approved Pembrolizumab for Bladder Cancer but it has been approved for other uses.
This is the first time that B-701 in combination with Pembrolizumab will be given to humans.
In this research study, Investigators are...
Testing the effectiveness and safety of the combination of two experimental drugs (B-701 and Pembrolizumab);
Learning about the good and/or bad effects the drugs have on participants and their cancer;
Administering B-701 and Pembrolizumab, which are antibodies (proteins that bind to other molecules), because...
Treating participants with Pembrolizumab, which is approved by the FDA for the treatment of Metastatic Melanoma, a Cancer of the skin;
Collecting blood and tissue samples and other related medical information to learn more about the development of cancer and predictors of response;
And hoping to learn how the combination of study drugs work in the treatment of cancer to help develop new treatments.
Inclusion Criteria:
Participants must have Stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or transitional cell carcinoma (TCC) arising in another location of the urinary tract, including urethra, ureter, and renal pelvis. The diagnosis must be histologically or cytologically confirmed. Mixed histologies are permitted as long as TCC is the major component (i.e. > 50% of the pathologic specimen). Pure or predominant squamous cell carcinomas or adenocarcinomas are not permitted.
Relapsed after or refractory to one or two prior lines of chemotherapy for advanced or metastatic/recurrent disease (at least one cycle each) which have not included a PD-L1 or FGFR inhibitor. At least one regimen should have included a platinum agent unless contraindicated for the subject. Prior neoadjuvant or adjuvant chemotherapy (without a PD-L1 or FGFR inhibitor) is permitted and will not be counted as first-line chemotherapy, as long as the subject has not progressed within 12 months of the last dose. However, a regimen of neoadjuvant or adjuvant chemotherapy will be counted as first-line chemotherapy if the patient progressed within 12 months of the last dose.
Age ≥ 18 years
Eastern cooperative oncology group (ECOG) performance status ≤ 1 (Karnofsky ≥ 60%)
Participants must have normal organ and marrow function as defined below:
Note: Screening labs should be performed within 10 days of treatment initiation.
Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (such conditions should be discussed with the subject before study entry)
The effects of B-701 on the developing human fetus are unknown. For this reason and because PD-1 inhibitors such as pembrolizumab may potentially cause fetal harm, women of child-bearing potential (defined as those who have not been surgically sterilized or have not been free from menses for > 1 year) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.
Female of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medications. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study and through 4 months after the last dose of study medication.
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Participants who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
Participants who are receiving, or have received, any other investigational drugs or devices within the 2 weeks prior to the first dose of study medications.
Participants who received major surgery must be recovered adequately from the toxicity and/or complications from the interventions prior to starting therapy.
Participants with a diagnosis of immunodeficiency or who are receiving systemic steroid therapy (>5 mg prednisone or its equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
Participants who have a primary central nervous system (CNS) malignancy, or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Individuals with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
Participants with a history of allergic reactions attributed to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
Participants with active autoimmune disease that has required systemic treatment (>5 mg of prednisone or its equivalent) in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Participants with known evidence of active, non-infectious pneumonitis.
Participants with an active infection requiring systemic therapy.
Participants who have received a live vaccine within 30 days of planned start of study therapy.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.