Avelumab in Combination With AVB-S6-500 in Patients With Advanced Urothelial Carcinoma

NCT04004442 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OU-SCC-COAXIN
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test the safety of avelumab and AVB-S6-500 and see what effects (good and bad) this combination treatment has on patients with advanced urothelial carcinoma.

Conditions

Urothelial Carcinoma

Keywords

avelumab; AVB-S6-500; renal pelvis cancer; ureter cancer; urinary bladder cancer; urethra cancer

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  To investigate the safety and tolerability of the study drug combination for Avelumab with AVB-S6-500

  up to 2 years

Secondary Outcomes (5)

• Progression Free Survival

  up to two years

• Clinical Benefit Rate

  up to two years

• Duration of Response

  up to two years

• Overall Survival

  up to two years

• Investigator assessed Objective Response Rate

  up to 2 years

Study Arms (1)

Avelumab + AVB-S6-500

EXPERIMENTAL

Drug: Avelumab; Drug: AVB-S6-500

Interventions

Avelumab DRUG

Avelumab: 800 mg IV every two weeks (on days 1 and 15 of a 28-day cycle)

Avelumab + AVB-S6-500

AVB-S6-500 DRUG

AVB-S6-500: 10mg/kg IV every 2 weeks (on days 1 and 15 of a 28-day cycle) Potential dose reduction: AVB-S6-500: 5mg/kg IV weekly (on days 1, 8, 15 and 22 of a 28-day cycle)

Avelumab + AVB-S6-500

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Histologically confirmed locally advanced unresectable (T4b or N2/N3 disease) or metastatic urothelial cancer (including renal pelvis, ureters, urinary bladder, urethra).
• Eligible patients must have had either:
• Progressed after treatment with at least 1 prior platinum-containing regimen, (e.g., received at least 2 cycles of cisplatin or carboplatin-based regimen) for inoperable locally advanced unresectable or metastatic urothelial carcinoma, OR OR
• Experienced disease progression or recurrence within 12 months of completion of neoadjuvant or adjuvant cisplatin-based chemotherapy, OR OR
• Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology group (ECOG) performance status 2, grade ≥2 neuropathy, GFR\<60 mL/min, grade ≥2 hearing loss or New York Heart Association class III or worse congestive heart failure.
• Declined platinum (cisplatin or carboplatin) based chemotherapy after informed discussion with the treating investigator
• Available pretreatment baseline tumor specimen or willingness to undergo biopsy of primary or metastatic lesion if archived specimen is not available.
• ECOG performance status of ≤2
• At least one measurable lesion by RECIST version 1.1
• Patients who are able to understand and sign the informed consent form.
• Ability to comply with protocol
• Adequate hematologic and end-organ function per protocol
• For women of childbearing potential: Negative serum or urine pregnancy test at screening.
• For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 30 days after the last dose of study drug

You may not qualify if:

• Concurrent systemic treatment with an anticancer treatment or investigational drug within 28 days. Palliative radiation to symptomatic primary tumor or metastases is permitted as long as there are other measurable lesions present outside of the radiation field.
• Prior therapy with anti-PD-1 or PD-L1 agents.
• Concurrent systemic therapy with corticosteroids (\>10 mg prednisone equivalent) or other immunosuppressive agents within 28 days before starting trial drug. Short-term administration of systemic steroids (less than 7 days), adrenal replacement steroid doses (≤10 mg daily prednisone equivalent), topical, intranasal and inhaled steroid use is permitted.
• Patients with untreated or symptomatic central nervous metastases will be excluded. Patients appropriately treated with either surgery and/or radiation therapy will be eligible to participate in the study 4 weeks after completion of radiation/surgery and if follow up brain imaging after CNS directed therapy demonstrates stability or improvement in brain metastases.
• Prior organ transplantation, including allogenic stem-cell transplantation.
• Known history of HBV infection (including acute and chronic infection) and untreated hepatitis C. Patients with treated HCV infection will be eligible.
• Known hypersensitivity to monoclonal antibody or any biologic drug, history of anaphylaxis, or uncontrolled asthma.
• Persisting toxicity related to prior therapy that was \> grade 1 according to NCI-CTCAE v4; grade ≤2 sensory neuropathy is allowed.
• Pregnant or lactating, or intending to become pregnant during the study
• a. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative pregnancy test result within 14 days prior to the first dose of study treatment.
• Diagnosis of active autoimmune disease requiring systemic immunosuppression. Patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring systemic immunosuppression are eligible.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• a. History of radiation fibrosis in the radiation field (fibrosis) is permitted.
• Active infection requiring systemic therapy.
• Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia

Sponsors & Collaborators

• University of Oklahoma: lead
• Aravive, Inc.: collaborator
• EMD Serono: collaborator

Study Sites (1)

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urethral Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ureteral Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Urethral Diseases

Study Officials

• Abhishek Tripathi, MD

  Stephenson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 2, 2019
• Study Start: February 17, 2020
• Primary Completion: April 7, 2022
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)