Study of NIVOLUMAB/IPILIMUMAB Maintenance in Unresectable Locally Advanced or Metastatic Urothelial Cancer

NCT05219435 | Completed Phase 2

• 2 other identifiers: SOGUG-2021-IEC(VEJ)-42021-005364-22
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 12

Brief Summary

Immunotherapy has improved clinical outcomes in metastatic urothelial carcinoma (mUC). Second-line treatment after progression to platinum-containing chemotherapy with immune checkpoint inhibitors (ICIs) have antitumor activity in advanced / metastatic UC and provide favorable safety profiles when compared with chemotherapy The study aims to determine if Nivolumab plus Ipilimumab maintenance therapy is effective in delaying disease progression in patients with unresectable locally advanced or metastatic urothelial cancer that did not progress during or following completion of first-line chemotherapy. Vexillum plans to recruit patients that achieve clinical benefit from first-line chemotherapy and may be candidates for maintenance immunotherapy to consolidate this benefit.

Conditions

Urothelial Cancer

Keywords

metastatic; unresectable locally advanced

Outcome Measures

Primary Outcomes (2)

• progression-free survival (PFS)

  PFS is defined as the time from the first dose of study treatment date until the first documentation disease progression or death from any cause, whichever occurs first. A subject who has not confirmed progression will be censored at the last known disease evaluation. Patients who have not progressed and start a new line of treatment will be censored at the date of the last adequate tumor assessment prior to starting the next line of therapy. Estimated by Kaplan Meier.

  Throughout the study period, approximately 12 months per patient from first study dose.

• progression-free survival (PFS) in PL-D1 positive patients

  subgroup analysis of PFS. Same definition of PFS as Outcome 1 applies.

  Throughout the study period, approximately 12 months per patient from first study dose.

Secondary Outcomes (9)

• Overall Survival (OS)

  Throughout the study period, approximately 12 months per patient from first study dose.

• Clinical benefit rate (CBR)

  Throughout the study period, approximately 12 months per patient from first study dose.

• Duration of response (DoR)

  Throughout the study period, approximately 12 months per patient from first study dose.

• Post-chemotherapy PFS (cPFS)

  Throughout the study period, approximately 12 months per patient from first study dose.

• Post-chemotherapy OS (cOS)

  Throughout the study period, approximately 12 months per patient from first study dose.

Study Arms (1)

Nivolumab plus Ipilimumab

EXPERIMENTAL

Patients will receive maintenance therapy with 4 cycles of Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg every three weeks (Q3W)(induction phase) followed by Nivolumab 480 mg every 4 weeks (Q4W)(consolidation phase) until unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab at 1 mg/kg by intravenous (IV) infusion on D1 of each cycle. Nivolumab at a fixed dose of 480 mg by intravenous (IV) infusion on D1 of each cycle. The maximum duration of treatment with nivolumab will be 2 years, and patients will discontinue treatment at any time in case of unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

Also known as: Opdivo

Nivolumab plus Ipilimumab

Ipilimumab DRUG

Ipilimumab at 3 mg/kg by intravenous (IV) infusion on D1 of each cycle.

Also known as: Yervoy

Nivolumab plus Ipilimumab

Eligibility Criteria

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

You may qualify if:

• \. Male or female subjects ≥ 18 years old.
• Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium.
• Also termed urothelial cell carcinoma \[UCC\] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra).
• Stage IV disease (T4b, N0, M0; any T, N1-N3, M0; any T, any N, M1) at the start of first line chemotherapy.
• Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine plus cisplatin and/or gemcitabine plus carboplatin.
• Tumor tissue (formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition) must be available at baseline.
• Note: Fine Needle Aspiration \[FNA\] and bone metastases samples are not acceptable. If an insufficient amount of tumor tissue from an unresectable or metastatic site is available prior to the start of the screening phase, subjects must consent to allow the acquisition of additional tumor tissue. This may be discussed with the PI if a new biopsy is feasible.
• Patients with adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL.
• Absolute neutrophil count (ANC) \> 1500 per mm3.
• Platelet count ≥ 100,000 per mm3.
• Serum bilirubin ≤ 1.5 X institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be ≤ 2X ULN. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology); however, they will be allowed only in consultation with their physician.
• Serum transaminases (ALT, AST and GGT) ≤ 2.5X institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 3X ULN.

You may not qualify if:

• ECOG performance status of \>1 (Karnofsky \< 70%).
• Patients whose disease progressed by RECIST v1.1 on or after first-line chemotherapy for urothelial cancer in the advanced or metastatic setting.
• Prior immunotherapy with IL-2, IFN-a or treatment with any immune checkpoint inhibitor therapy (e.g, CTLA4, PD-1, or PD-L1 targeting agent) for the unresectable metastatic setting.
• Note: Patients may have received immunotherapy in the adjuvant setting as long as the last dose of adjuvant was administered at least 12 months prior to the first dose of trial treatment.
• Receipt of any type of systemic chemotherapy or anticancer therapy within 3 weeks before starting treatment.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• History of allogeneic organ transplant.
• Any non-cancer treatment with vaccines used for the prevention of infectious diseases (up to 1 month before or after any dose of ipilimumab and nivolumab).
• Major surgery (i.e. cystectomy) less than 28 days prior to the first dose of study treatment.
• Subjects that have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of trial treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid).
• Active or prior documented autoimmune disease within the past 2 years which requires systemic therapy.
• Note: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Subjects with Type I diabetes mellitus are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis).
• Inadequate haematological/organ function.
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or symptomatic pulmonary embolism.

Sponsors & Collaborators

• Spanish Oncology Genito-Urinary Group: lead
• Bristol-Myers Squibb: collaborator

Study Sites (12)

Hospital Universitario Juan Ramón Jiménez

Huelva, Andalusia, 21005, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, Andalusia, 41009, Spain

Location

Hospital Clínico Universitario de Zaragoza

Zaragoza, Aragon, 50009, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Complejo asistencial universitario de Salamanca

Salamanca, Castille and León, 37007, Spain

Location

Hospital Universitario de Toledo

Toledo, Castille-La Mancha, 45004, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, Galicia, 15706, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitario de la Ribera

Alzira, Valencia, 46600, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Guillermo de Velasco

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

Study Design

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

Model Details: Patients will receive maintenance therapy with 4 cycles of Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg every three weeks (Q3W)(induction phase) followed by Nivolumab 480 mg every 4 weeks (Q4W)(consolidation phase) until unacceptable toxicity, disease progression (PD), investigator ́s decision, patient's consent withdrawal or death by any cause, whichever occurs first.

Study Record Dates

• First Submitted: January 21, 2022
• First Posted: February 2, 2022
• Study Start: July 6, 2022
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12)