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

NCT02717156 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 4B-15-11NCI-2016-00147P30CA014089
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 9

Brief Summary

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. 1.Cohort A, phase II 2nd line trial of sEphB4-HSA and pembrolizumab for platinum refractory metastatic urothelial carcinoma.
2. 2.Cohort B, phase II 3rd line trial of sEphB4-HSA and pembrolizumab for platinum refractory metastatic urothelial carcinoma.
3. 3.Cohort C, phase II neoadjuvant trial of sEphB4-HSA and pembrolizumab for locally advanced muscle invasive urothelial carcinoma.
4. 4.Cohort D, phase II neoadjuvant trial of sEphB4-HSA and pembrolizumab for locally advanced prostate cancer.

Conditions

Stage IV Bladder Urothelial Carcinoma; Prostate Cancer; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of toxicities and adverse events classified according to the Common Terminology Criteria for Adverse Events v4.03

  All observed toxicities will be summarized in terms of type (organ affected or laboratory determination, severity, and time of onset. Tables will be created to summarize these toxicities and side effects, overall and by course. The proportion of patients who are eligible to begin the 3rd planned cycle will be calculated, using the number of eligible patients who began treatment as the denominator; 95% confidence intervals will be constructed.

  Up to 30 days

Secondary Outcomes (1)

• OR defined as complete response or partial response according to RECIST v 1.1

  Up to 3 years

Study Arms (1)

Treatment (EphB4-HSA and pembrolizumab)

EXPERIMENTAL

Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Procedure: Computed Tomography; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Biological: Recombinant EphB4-HSA Fusion Protein

Interventions

Computed Tomography PROCEDURE

Correlative studies

Also known as: CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography, CT, CT SCAN, tomography

Treatment (EphB4-HSA and pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (EphB4-HSA and pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (EphB4-HSA and pembrolizumab)

Positron Emission Tomography PROCEDURE

Correlative studies

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (EphB4-HSA and pembrolizumab)

Recombinant EphB4-HSA Fusion Protein BIOLOGICAL

Given IV

Also known as: sEphB4-HSA

Treatment (EphB4-HSA and pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 30mL/min for subject with creatinine levels \> 1.5 X institutional upper limit of normal (ULN)
• Serum total bilirubin =\< 1.5 X ULN or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN or =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
• Female subject of childbearing potential should have a negative urine or serum pregnancy; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential must be willing to use adequate method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

Location

LAC+USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology - Newport Beach

Newport Beach, California, 92663, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66205, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Levine Cancer Institute-Carolinas Medical Center

Charlotte, North Carolina, 28277, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Sadeghi S, Quinn D, Dorff T, Pal S, Groshen S, Tsao-Wei D, Parikh R, Devitt M, Parikh M, Jackovich A, Ruel N, Vogelzang N, Burgess E, Siddiqi I, Gill IS, Lara PN, Dreicer R, Gill PS. EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma. J Clin Oncol. 2023 Jan 20;41(3):640-650. doi: 10.1200/JCO.21.02923. Epub 2022 Aug 19.

  PMID: 35984996 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Carcinoma, Transitional Cell

Interventions

pembrolizumab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Sarmad Sadeghi, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 23, 2016
• Study Start: November 21, 2016
• Primary Completion: November 21, 2025
• Study Completion (Estimated): November 21, 2026
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

US (9)