Avelumab Short Maintenance Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-01-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Erasmus MC Cancer Institute

External identifiers

EU CT number

2024-512975-11-01

EudraCT number

2020-005781-34

ClinicalTrials.gov

NCT20200057

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic

To demonstrate the benefit of maintenance treatment with a maximum of six months
avelumab in increasing the overall survival (OS) at 18 months in patients with unresectable locally
advanced or metastatic UC whose disease did not progress on or following completion of first-line
platinum-containing chemotherapy

Secondary objectives 1

1. PRO, clinical outcome in subgroups

Conditions and MedDRA coding

urothelial cancer

Regulatory references

Plan to share IPD

Yes

IPD plan description

See protocol for detailed informed.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients must meet all ofthe following inclusion criteria to be eligible for enrolment into the study: 1. Diagnosis: a. Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium. b. Documented Stage IV disease (T4b, NO, M0; any T, N1—N3, MO; any T, any N, M1) atthe start of first-line chemotherapy. 2. Priorfirst-line chemotherapy must have consisted of atleast 4 cycles and nomore than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin. No other chemotherapy regimens are allowed in thisstudy. 3. Patients without progressive disease as per RECIST v1.1 guidelines (ie, with an ongoing CR, PR, or SD) following completion of 4 to 6 cycles of first-line chemotherapy. 4. Evidence of a signed and dated informed consent document indicating that the patient (or a legally acceptable representative, as allowed by local guideline/practice) has been informed of all pertinent aspects ofthe study. 5. Plasma samples: Provision of a plasma sample prior to the 4” cycle is mandatory 6. Patients who are willing and able to comply with scheduled visits,treatment plans, laboratory tests, and otherstudy procedures. 7. Age; Minimum of 18 years 8. Estimated life expectancy of at least 3months. 9. Eastern Cooperative Oncology Group (ECOG) performance status(PS) 0 or 1 (Appendix 1). Pagina 24 van 62 NL75848.056.20/ Ave-short-trial 10. Adequate bone marrow function, including: a. Absolute neutrophil count (ANC) 1,500/mm3 or 1.5 x 109/L; b. Platelets 100 x 109/L; c. Hemoglobin 5.6 mmol/L (may have been transfused). 12. Adequate renal function, defined as estimated creatinine clearance 30mL/min as calculated using the Cockcroft-Gault equation 13. Adequate liver function, including: a. Totalserum bilirubin 1.5 x upper limit of normal (ULN); b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)2.5 x ULN. 14. Male patients able to father children and female patients of childbearing potential and atrisk for pregnancy must agree to use 2 highly effective methods of contraception (Section 4.3.1) throughout the study and for at least g0 days after the last dose of assigned treatment.

Exclusion criteria 1

1. Patients with any ofthe following characteristics/conditions will not be included in the study: 1. Patients whose disease progressed by RECIST v1.1 onor afterfirst-line chemotherapy for urothelial cancer. 2. Prior adjuvant or neoadjuvant therapy within 12 months of initiation of avelumab. 3. Prior immunotherapy with IL-2, IFN-y.-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 4. Patients with known symptomatic central nervoussystem (CNS) metastasesrequiring steroids. Patients with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy orsurgery prior to initiation of avelumab, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable. 5. Persisting toxicity related to prior therapy or recently initiated avelumab NCI CTCAE v5.0 Grade >1; however, sensory neuropathy Grade 2 is acceptable. 6. Diagnosis of any other malignancy within 5 years prior to initiation of avelumab, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, orlow-grade (Gleason 6) prostate cancer on surveillance without any plansfortreatment intervention (eg,surgery, radiation, or castration). 7. Participation in other studies involving investigational drug(s) within 4 weeks prior to initiation of avelumab. Observational studies are permitted. 8. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypoor hyperthyroid disease not requiring immunosuppressive treatment are eligible. Pagina 25 van 62 NL75848.056.20 / Ave-short-trial 9. Any ofthe following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft,symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack. 10. Active infection requiring systemic therapy. 11. Known severe hypersensitivity reactionsto monoclonal antibodies(Grade 3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of asthma symptom control per the Global Initiative for Asthma 2015). 62 12. Known prior orsuspected hypersensitivity to avelumab 13. Current use of immunosuppressivemedication, EXCEPT the following: a. Intranasal, inhaled, topical steroids, or localsteroid injections (eg, intra-articular injection); b. Systemic corticosteroids at(equivalent) doses ofmaximum 10 mg prednisone c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 14.Diagnosis of priorimmunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. 15. Any test for hepatitis B virus (HBV) or hepatitis C virus(HCV) indicating acute or chronic infection. 16.Vaccination within 4 weeks of the first dose ofstudy treatment and while on trial is prohibited except for administration of inactivate vaccines (for example, inactivated influenza vaccines) or mRNA vaccines (for example, COVID-19 vaccines) 17. Pregnant female patients; breastfeeding 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 as outlined in the protocol for the duration ofthe study and for atleast 90 days afterthe last dose of avelumab. 18. Othersevere acute or chronic medical conditionsincluding colitis, inflammatory bowel disease, and pneumonitis; psychiatric condition including recent(within the past year) or active suicidal ideation or behaviour; or laboratory abnormality that may increase the risk associated with study participation ors

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 18months overallsurvival (OS)

Secondary endpoints 1

1. OS in PD-L1 positive and PD-L1 negative tumors, in patients with visceral versus non-visceral metastases, in patients with CR/PR as best response to chemotherapy versus SD, and in retreated patients. PFS in PD-L1 positive and PD-L1 negative tumors, and in retreated patients. ORR per RECIST 1.1 in retreated patients. Duration ofresponse. Disease control (defined as complete response, partial response, non—complete response or non-progressive disease, orstable disease at 24 weeks after initi

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Youssra Salhi

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Youssra Salhi

Locations

1 EU/EEA country · 17 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 5 files

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

Application history

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