ACTIVE_NOT_RECRUITING

Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors

Conditions

Stage IV Bladder Urothelial Carcinoma Prostate Cancer Urothelial Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a multi-cohort single arm phase II/screening trial of the combination of a fusion protein that binds EphrinB2 and blocks interaction with cell surface EphB receptors (sEphB4-HSA) in combination with an anti-PD1 antibody (MK-7435 / Pembrolizumab) for treatment of patients with specific solid tumors. There will be four cohorts in this trial: 1. Cohort A, phase II 2nd line trial of sEphB4-HSA and pembrolizumab for platinum refractory metastatic urothelial carcinoma. 2. Cohort B, phase II 3rd line trial of sEphB4-HSA and pembrolizumab for platinum refractory metastatic urothelial carcinoma. 3. Cohort C, phase II neoadjuvant trial of sEphB4-HSA and pembrolizumab for locally advanced muscle invasive urothelial carcinoma. 4. Cohort D, phase II neoadjuvant trial of sEphB4-HSA and pembrolizumab for locally advanced prostate cancer.

Official Title

A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-3475) for Solid Tumors

Quick Facts

Study Start:2016-11-21

Study Completion:2026-11-21

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT02717156

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment * 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 a known history of active TB (bacillus tuberculosis) * Hypersensitivity to pembrolizumab or any of its excipients * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (ie, =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability * 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 known history of, or any evidence of active, non-infectious pneumonitis * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA * Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) * Has known active Hepatitis B (eg, hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C (eg, hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected) * 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 (MK-3475) 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 (eg, 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 in the office, may be considered eligible if blood pressure log at home is within acceptable limits AND upon review and agreement from the Sponsor.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
* 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 a known history of active TB (bacillus tuberculosis)
* Hypersensitivity to pembrolizumab or any of its excipients
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (ie, =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
* 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 known history of, or any evidence of active, non-infectious pneumonitis
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA
* Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
* Has known active Hepatitis B (eg, hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C (eg, hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
* 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 (MK-3475) 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 (eg, 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 in the office, may be considered eligible if blood pressure log at home is within acceptable limits AND upon review and agreement from the Sponsor.

Contacts and Locations

Principal Investigator

Sarmad Sadeghi, MD

PRINCIPAL_INVESTIGATOR

University of Southern California

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

LAC+USC Medical Center

Los Angeles, California, 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

USC Norris Oncology/Hematology - Newport Beach

Newport Beach, California, 92663

United States

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

University of Kansas Cancer Center

Kansas City, Kansas, 66205

United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169

United States

Levine Cancer Institute-Carolinas Medical Center

Charlotte, North Carolina, 28277

United States

University of Virginia Cancer Center

Charlottesville, Virginia, 22908

United States

Collaborators and Investigators

Sponsor: University of Southern California

Sarmad Sadeghi, MD, PRINCIPAL_INVESTIGATOR, University of Southern California

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2016-11-21

Study Completion Date2026-11-21

Study Record Updates

Study Start Date2016-11-21

Study Completion Date2026-11-21

Terms related to this study

Additional Relevant MeSH Terms

Stage IV Bladder Urothelial Carcinoma
Prostate Cancer
Urothelial Carcinoma