Maintenance AVElumab after SECond line platinum-based chemotherapy for metastatic urothelial carcinoma: AVESEC trial – GOIRC-02-2025

Overview

Sponsor-declared trial summary

Key facts

Sponsor

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Healthcare KGaA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective is to assess the efficacy in terms of blinded independent central review (BICR) progression-free survival (PFS) of maintenance avelumab 800 mg IV Q2W vs best supportive care (BSC) in patients with partial/complete response or stable disease to second-line platinum-based chemotherapy with advanced or metastatic urothelial carcinoma progressed to first-line pembrolizumab plus enfortumab vedotin

Secondary objectives 5

1. To determine the benefit in terms of overall survival (OS) of maintenance avelumab vs BSC
2. To determine the benefit in terms of PFS assessed by investigator of maintenance avelumab vs BSC.
3. To evaluate the anti-tumor activity of maintenance avelumab vs BSC according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
4. To evaluate the overall safety profile of maintenance avelumab vs BSC.
5. To assess the effect of maintenance avelumab vs BSC on patients reported outcomes (PROs) using 2 validated instruments (FBlSI and EQ-5D).

Conditions and MedDRA coding

metastatic urothelial carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically or cytologically-confirmed diagnosis of metastatic or locally advanced unresectable urothelial carcinoma of the bladder or upper tract with predominant transitional cell carcinoma.
2. Have received first-line of therapy consisting in enfortumab vedotin plus pembrolizumab and second-line of therapy with cisplatin or carboplatin plus gemcitabine (at least 3 cycles). Adjuvant or neoadjuvant chemotherapy is allowed if completed by >12 months.
3. Have not progressed per RECIST v1.1 guidelines (stable disease, partial response, complete response) following completion of 3-6 cycles of second-line chemotherapy.
4. Have measurable disease by RECIST v1.1 as assessed by the investigator
5. Estimated life expectancy of at least 3 months.
6. Willing and able to comply to study visits and procedures and be available for the duration of the study.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
8. Adequate organ and bone marrow function, including: a. Absolute neutrophil count (ANC) ≥1,500/mm3 or 1.5 x 109/L ; b. Platelets ≥100,000/mm3 or 100 x 109/L; c. Hemoglobin ≥9 g/dL (may have been transfused); d. Estimated creatinine clearance ≥30 mL/min calculated using the Cockcroft-Gault equation; e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN); f. Total bilirubin ≤1.5 x ULN. For subjects with Gilbert's disease, ≤3 mg/dL.
9. Serum pregnancy test (for females of childbearing potential) negative at screening.
10. If in fertile age, must agree to use highly effective methods of contraception (licensed hormonal methods for female patients and condom for male patients) throughout the study and for at least 30 days after the last dose.
11. Male or female ≥18 years.
12. Signed informed consent documenting that the patient has been informed on all the aspects of the study.
13. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria

Exclusion criteria 17

1. Patients whose disease progressed by RECIST v1.1 on second-line chemotherapy for urothelial cancer
2. Prior grade ≥3 per National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) toxicity from an immune-checkpoint inhibitor (thyroid toxicity excluded).
3. Persisting toxicity related to prior therapy (CTCAE Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable
4. Patients with known symptomatic central nervous system (SNC) metastases requiring steroids. Patients are eligible if treatment (radiation or surgery) for SNC metastases has been completed by at least 4 weeks before first study dose and have recovered from acute effects of treatment and are neurologically stable.
5. Has had major surgery within 4 weeks prior to first study dose. Complete wound healing must have occurred independently from the time passed
6. Has received prior radiotherapy within 2 weeks prior to first study dose. Prior palliative radiotherapy to metastatic bone lesion(s) is permitted, provided it has been completed at least 48 hours prior to first study dose.
7. Active autoimmune disease requiring high-dose steroids or immunosuppressive treatment. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
8. Diagnosis of any other malignancy within 5 years prior to randomization, except for radically treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6) prostate cancer on surveillance
9. Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization with the exception of observational studies
10. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
11. Known prior severe hypersensitivity to study drug or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE Grade ≥3).
12. Current or prior use of immunosuppressive medication within 7 days prior to randomization, EXCEPT the following: a) intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); b) systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c) steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
13. Active and/or uncontrolled infection. The following exceptions apply: a. Participants with HIV infection are eligible if they are on effective antiretroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction. b. Participants with evidence of chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), and if they have ALT, AST, and total bilirubin levels < ULN, and provided there is no expected drug-drug interaction. c. Participants with a history of HCV infection are eligible if they have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load, and if they have ALT, AST, and total bilirubin levels < ULN.
14. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
15. Prior organ transplantation including allogenic stem-cell transplantation
16. Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (eg, inactivated influenza vaccines)
17. Pregnant or lactating female patients; male patients able to father children, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception for the duration of the study and for at least 60 days after the last dose of study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Comparison between treatment arms will be performed using a one-sided log-rank test, and the treatment effect will be quantified using the hazard ratio (HR) estimated from a Cox proportional hazards model, along with corresponding confidence intervals.

Secondary endpoints 8

1. Investigator-assessed PFS
2. Objective response rates (ORR)
3. Duration of response (DR)
4. Disease control rate (DCR) assessed per RECIST v1.1 by BICR and investigator.
5. Safety: Adverse events (AEs) and laboratory abnormalities as graded by Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
6. Patient-Reported Outcomes: patient-reported bladder cancer symptom, functioning, global quality of life (QOL), and Time to Deterioration (TTD) using the NCCN- FACT FBlSI; health status using the EQ-5D.
7. Overall Survival (OS)
8. 1-year PFS based on BICR assessment per RECIST v1.1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Sponsor organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Address

Viale Antonio Gramsci 14

City

Parma

Postcode

43126

Country

Italy

Scientific contact point

Organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Coordinating Investigator - Francesco Massari

Public contact point

Organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Coordinating Investigator - Francesco Massari

Third parties 1

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications