Combining Pembrolizumab and sEphB4 for advanced bladder cancer

A Phase II Trial of Pembrolizumab as Standard of Care + sEphB4-HSA in Chemotherapy Ineligible or Chemotherapy Refusing Patients With Metastatic Urothelial Carcinoma

This study is testing if combining the immunotherapy drug Pembrolizumab with sEphB4 can help people with advanced bladder cancer who can't have chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vasgene Therapeutics, Inc (Industry-sponsored)
• Drugs / interventions: pembrolizumab, chemotherapy
• Locations: 1 site (Santa Monica, California)
• Trial ID: NCT04486781 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of combining Pembrolizumab, an immunotherapy drug, with sEphB4-HSA, which may inhibit tumor growth and blood vessel formation, in patients with advanced metastatic urothelial carcinoma who cannot receive chemotherapy. Participants will receive these treatments through intravenous infusions over a series of cycles, with the possibility of continuing as long as they respond positively and remain stable. The study aims to provide an alternative treatment option for those who are treatment naïve and refuse or are ineligible for chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with untreated advanced metastatic urothelial carcinoma who are ineligible for or refuse chemotherapy.

Not a fit: Patients with non-urothelial carcinoma or those who have previously received treatment for their cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could offer a new treatment option for patients with advanced bladder cancer who are unable to undergo traditional chemotherapy.

How similar studies have performed: While the combination of immunotherapy and targeted agents is a growing area of interest, this specific combination of Pembrolizumab and sEphB4-HSA is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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 treatment.
* 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.

Where this trial is running

Santa Monica, California

• Sarcoma Oncology Center — Santa Monica, California, United States (Recruiting)

Study contacts

• Principal investigator: Sarmad Sadeghi, MD — University of Southern California
• Study coordinator: Jon Cogan, MS

Conditions Metastatic Urothelial Carcinoma