A Phase 2, open-label, multi-centre, multi-national interventional trial to evaluate the efficacy and safety of erdafitinib (ERDA) monotherapy and erdafitinib (ERDA) and cetrelimab (CET) combination as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) whose tumours express FGFR gene alterations (SOGUG-NEOWIN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grupo Espanol De Oncologia Genitourinaria-Socug

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Dec 2023 → ongoing

Decision date (initial)

2024-09-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Pharmaceutica NV

External identifiers

EU CT number

2024-512573-27-01

EudraCT number

2022-002586-15

ISRCTN

ISRCTN14498712

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

• To assess the antitumor activity measured as pT0N0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen.
• To assess the percentage of pathological downstaging response < ypT2

Secondary objectives 6

1. 1. To evaluate the percentage of tumour downstaging, defined as pathological TNM less than clinical TNM
2. 2. To estimate the event-free survival (EFS) rate, defined as disease progression, death or any event that prevents the performance of RC, including initiation of any additional therapy prior to RC.
3. 3. To estimate the overall survival (OS).
4. 4. To evaluate the Objective Response Rate (ORR) according to RECIST v1.1 in subjects after neoadjuvant treatment (previous to RC).
5. 5. To assess the safety profile and tolerability of both schemes of erdafitinib alone and in combination with cetrelimab.
6. 6. To calculate the rate of delay of surgery.

Conditions and MedDRA coding

Muscle-invasive bladder cancer (MIBC)

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study.
2. 2. Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal TURBT performed no later than 3 months prior to start the screening visit.
3. 3. Pure or predominant (≥50%) UC histology as determined at the local site.
4. 4. Age ≥ 18 years.
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. 6. Decline or ineligible (“unfit”) for cisplatin-based chemotherapy as defined by any one of the following criteria: a. Impaired renal function (glomerular filtration rate [GFR] ≥ 30 but < 60 mL/min). GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. b. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 ≥ Grade 2 hearing loss (assessed per local standard of care). c. CTCAE, Version 5.0 ≥ Grade 2 peripheral neuropathy. d. Any other reason to be ineligible for cisplatin should be consulted with the coordinating PI.
7. 7. Presence of a selected FGFR alteration on analysis of tumour biopsy. Local reports based on validated tests can be accepted (with subsequent confirmation by Central Laboratory). Patients having positive local testing will not have to wait for confirmation to be enrolled. It is required fromall patients to send tumour sample to Central Laboratory to analyse DNA mutations and RNA fusion by Next Generation Sequencing and eCounter, respectively. In case of discrepancies, the local determination will prevail.
8. 8. Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to Cycle 1 Day 1 (medical management allowed): a. Absolute Neutrophil Count (ANC) ≥1.5 x 109/L. b. Platelets ≥100 x 109/L. c. Haemoglobin ≥9 g/dL (5.6 mmol/L). d. International normalized ratio (INR) or Prothrombin time (PT) ≤1.5 x ULN e. Total bilirubin ≤1.5 x ULN except patients with Gilbert Syndrome, who must have a total bilirubin level of <3.0 x ULN. f. ALT and AST ≤2.5 x ULN g. Creatinine clearance ≥30 mL/min. h. Phosphate < Upper Limit of Normal (ULN)
9. 9. No other malignancy (diagnosis within the last 3 years), except for treated non-melanoma skin cancer (basal or squamous), carcinoma in situ of cervix and low risk prostate cancer.
10. 10. Willingness to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of erdafitinib and/or 150 days after the last dose of cetrelimab, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriateprecautions to avoid pregnancy (with at least 99% certainty) from screening through 90 days after the last dose of erdafitinib and/or 150 days after the last dose of cetrelimab (Acceptable contraception is defined in Appendix 8). A WOCBP is a female who 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (has had at least menses at any time preceding 12 consecutive months). Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of aamenorrhea) are eligible.

Exclusion criteria 23

1. 1. Clinical evidence of N2-N3 tumours or metastatic bladder cancer.
2. 2. Has tumour with any neuroendocrine or small cell component.
3. 3. Patients who are not considered fit for cystectomy or reject cystectomy.
4. 4. Patients with co-morbidities that will preclude them from trial intervention.
5. 5. Prior FGFR-targeted or antiPD1/PDL1 systemic therapy.
6. 6. Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than transurethral resection of bladder tumour (TURBT) or biopsies is not permitted. Prior BCG or other intravesical treatment of non-MIBC is permitted if completed at least 6 weeks prior to initiating study treatment.
7. 7. Evidence of UC in upper urinary tracts (ureters or renal pelvis), prostatic urethra,history of previous MIBC or UC not confined to the bladder.
8. 8. Major surgical procedure within 14 days prior to the first dose or still recovering from prior surgery.
9. 9. Severe infection within 4 weeks prior to allocation.
10. 10. Uncontrolled adrenal insufficiency.
11. 11. True positive test results for hepatitis B, or C during screening.
12. 12. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
13. 13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring medication except for atrial fibrillation that is rate controlled with medication, myocardial infarction within 6 months of Cycle 1 Day 1, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
14. 14. Known allergy or hypersensitivity to study drug formulations.
15. 15. Known history of allergy to protein-based therapies or a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia).
16. 16. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment (RPED) of any grade.
17. 17. Inability to swallow and retain oral medication.
18. 18. History of calcium and phosphate homeostasis disorder or systemic mineral imbalance.
19. 19. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
20. 20. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
21. 21. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
22. 22. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
23. 23. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 480 ms is excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Pathological complete response (pCR)
2. Pathological downstaging < ypT2

Secondary endpoints 6

1. Rate of pathological downstaging (pDS)
2. Event-free Survival rate
3. OS
4. ORR according to RECIST, after neoadjuvant treatment
5. Adverse events
6. Rate of delay of surgery (classed as a delay event if performed > 6 weeks after last dose of treatment)

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grupo Espanol De Oncologia Genitourinaria-Socug

Sponsor organisation

Grupo Espanol De Oncologia Genitourinaria-Socug

Address

Calle De Velazquez 7 Floor 3

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Grupo Espanol De Oncologia Genitourinaria-Socug

Contact name

Trial Manager

Public contact point

Organisation

Grupo Espanol De Oncologia Genitourinaria-Socug

Contact name

SOGUG Secretary

Third parties 6

Locations

3 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 31 files

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

Application history

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