sEphB-HSA may prevent tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. The purpose of this study is to evaluate the combination of Pembrolizumab + sEphB4-HSA in the population of patients with previously untreated advanced (metastatic or recurrent) urothelial carcinoma who are chemotherapy ineligible or who refuse chemotherapy.
The combination of Pembrolizumab + sEphB4-HSA will be given through an intravenous infusion
(into a vein). Each cycle of sEphB4-HSA will be given at Day 1, 8, and 15 of each 3 week
cycle. Each cycle of Pembrolizumab will be given at Day 1 of each 3 week cycle.
Participants may continue on study protocol as long as they continue to respond and remains
clinically stable on study medication.
Patients may come off treatment for the following reasons:
- Disease progression.
- If tumor resolves.
- For participants who become pregnant.
- Incidence or severity of adverse drug reaction in this or other studies indicates a
potential health hazard to subjects.
- Patient withdraws consent.
- Study termination by the Sponsor.
- Participants who are non-compliant with respect to taking drugs, keeping appointments,
or having tests required for the evaluation of drug safety and efficacy.
- Participant's condition renders them unacceptable for further treatment in the judgment
of the investigator.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||December 31, 2020||Phase 2||Interventional|
Primary Outcome 1 - Measure: Estimate of the overall response rate (ORR) of the combination of Pembrolizumab + sEphB4-HSA in the patients with previously untreated advanced (metastatic or recurrent) urothelial carcinoma who are chemotherapy ineligible or who refuse chemotherapy
Primary Outcome 1 - Time Frame: At study entry until completion (average of 60 months)
- Be willing and able to provide written informed consent/assent for the trial.
- Age ≥ 18 years.
- Be treatment naïve and have advanced (metastatic or recurrent) pathologically proven
urothelial carcinoma. Patients progressing more than 12 months of their last dose of
platinum-based neoadjuvant or adjuvant chemotherapy are eligible.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function as defined in Table 1., all screening labs should
be performed within 10 days of treatment initiation.
- Be ineligible for chemotherapy in the assessment of the treating physician or refusing
chemotherapy in frontline setting. Cisplatin ineligibility is defined as Cresatinine
Clearance (CrCl) < 60cc/min, NYHA class III hear failure, grade II neuropathy and
grade II hearing loss, the latter two also apply to carboplatin-based chemotherapy.
- Be approved to begin treatment with pembrolizumab per standard of care and
pembrolizumab must be available to the patient. Patient must enroll on this study
prior to the receiving the second dose of pembrolizumab and prior to having restaging
imaging after receiving pembrolizumab. Other PD1/PDL1 antibodies are now allowed.
- Have measurable disease based on RECIST 1.1. We request an OPTIONAL core biopsy from
an accessible metastatic site after a minimum of 2 cycles of treatment AND prior to
progression of disease to help the investigators better understand the activity of
these drugs in tumor tissue.
In addition, we request an OPTIONAL collection of any surgical specimens obtained per
standard of care during the study. For instance, specimens from metastasectomy while
patient is undergoing therapy on this study.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
- Has a known history of active TB (Bacillus Tuberculosis)
- Has active autoimmune disease that has required systemic treatment 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.
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma potentially cured after surgery or prostate
cancer that is under control by hormonal agents.
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Treated brain metastases are allowed.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.
- Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute
coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive
pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any
other intercurrent medical condition that contraindicates treatment with sEphB4HSA or
pembrolizumab or places the patient at undue risk for treatment related complications.
- Has 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.
- Uncontrolled hypertension is excluded- systolic blood pressure >140mmHg or diastolic
>90mmHg. Patients experiencing white coat hypertension the office, may be considered
eligible if blood pressure log at home is within acceptable limits AND upon review and
agreement from the Sponsor.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Sant Chawla, MD
Role: Principal Investigator
Affiliation: Sarcoma Oncology