CV301 Combined With PD-1/L1 Blockade in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

NCT03628716 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CV301-BLD-001
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase 2, single-arm, multi-institutional clinical trial designed to study the combination of CV301 with atezolizumab in the first-line treatment of UC not eligible for cisplatin-containing chemotherapy (Cohort 1) and in the second-line treatment of UC previously treated with standard first-line cisplatin-based chemotherapy (Cohort 2).

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is the proportion of subjects in the analysis population with a Complete Response (CR) or Partial Response (PR) based on best overall RECIST v1.1 evaluations as performed by the investigator. According to RECIST v1.1, the sum of the longest diameters of non-nodal target lesions and short axis of nodal target lesions are used to evaluate tumor response. Maximum of 2 target lesions per organ and 5 target lesions are used for the measurement. CR means disappearance of all known disease, confirmed at 4 week, lymph nodes must be \< 10 mm short axis. PR means \>=30% decrease from baseline measurement, confirmed at 4 week.

  up to 24 months

Secondary Outcomes (10)

• Progression Free Survival (PFS)

  The time from day of first treatment to the start of disease progression or death, whichever occurs first, or the last assessment date if there is a lack of progression, up to 24 months for each subject or discontinuation of the study by sponsor.

• Overall Survival (OS)

  The time interval from first vaccination to death of any cause, up to 24 months for each subject or discontinuation of the study by sponsor.

• Duration of Response

  up to 24 months

• Treatment-Emergent Adverse Events

  up to 24 months

• Toxicity Grade Shift From Baseline in Laboratory Results

  Overall Study up to 24 months

Study Arms (1)

CV301 + Atezolizumab

EXPERIMENTAL

Subject receiving combination treatment with CV301 + Atezolizumab

Biological: CV301; Biological: Atezolizumab

Interventions

CV301 BIOLOGICAL

Prime with MVA-BN-CV301 (nominal titer 1.6 x 10\^9 Inf.U) given subcutaneously (SC) on Day 1 and Day 22. One dose = four 0.5 mL injections. One injection = nominal titer 4 x 10\^8 Inf.U in 0.5 mL. Boost with FPV-CV301 (nominal titer of 1 × 10\^9 Inf.U in 0.5 mL, given SC every 21 days for 4 doses (on days 43, 64, 85, and 106), followed by boosts every 6 weeks until 6 months on trial (i.e., days 148 and 190), then every 12 weeks until completion of 2 years. One dose = one 0.5 mL injection.

CV301 + Atezolizumab

Atezolizumab BIOLOGICAL

Atezolizumab fixed dose of 1200 mg intravenous on Day 1 of each 21-day cycle

CV301 + Atezolizumab

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 at date of ICF signature having the ability to comply with protocol.
• Histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) UC (including renal pelvis, ureters, urinary bladder, urethra)
• Patients with mixed histologies were required to have a dominant transitional cell pattern.
• Locally advanced bladder cancer that was inoperable on the basis of involvement of the pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3).
• Life expectancy ≥ 12 weeks.
• Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
• Demonstrate adequate organ function.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly) and to continue its use for 5 months after the last dose of atezolizumab.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or 10-15 unstained slides, with an associated pathology report.
• For Cohort 1:
• Untreated with chemotherapy
• Have at least one of the following:
• ECOG (Eastern Cooperative Oncology Group) performance status of 2.
• Glomerular filtration rate calculated as creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min and less than 60 mL/min
• Hearing loss or neuropathy of any cause Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2

You may not qualify if:

• Any approved anti-cancer therapy, including chemotherapy, within 3 weeks prior to initiation of trial treatment; the following exceptions are allowed:
• Palliative radiotherapy for bone metastases or non-target soft tissue lesions completed \>7 days prior to baseline imaging.
• Hormone-replacement therapy or oral contraceptives.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to screening given that all AEs related to prior treatment have resolved to baseline or Grade 1.
• Active central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments or Leptomeningeal disease.
• Uncontrolled tumor-related pain:
• Patients requiring pain medication must be on a stable regimen at trial entry.
• Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to trial entry.
• Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) could be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• a. Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled hypercalcemia (\>1.5 mmol/L ionized calcium or Ca \>12 mg/dL or corrected serum calcium \>ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab:
• Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who did not have a history of clinically significant hypercalcemia are eligible.
• Patients who are receiving denosumab prior to enrollment have to be willing and eligible to receive a bisphosphonate instead while in the trial.
• Malignancies other than urothelial carcinoma within 3 years prior to Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and no intent for further treatment or incidental prostate cancer (T1/T2b, Gleason score ≤7 undergoing active surveillance and treatment naive).

Sponsors & Collaborators

• Bavarian Nordic: lead

Study Sites (6)

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

Location

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Bavarian Nordic Call Center
• Organization: Bavarian Nordic A/S

medical.information_us@bavarian-nordic.com

1-844-422-8274

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 14, 2018
• Study Start: September 18, 2018
• Primary Completion: November 3, 2020
• Study Completion: February 2, 2021
• Last Updated: April 27, 2022
• Results First Posted: April 27, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)