Neoadjuvant Lu-PSMA radioligand therapy and Ipilimumab in men with very high-risk prostate cancer (NEPI)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Essen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

25 Aug 2025 → 9 Mar 2026

Decision date (initial)

2024-07-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514386-19-00

EudraCT number

2021-004894-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

Co-primary endpoints of the study are feasibility and safety.

Secondary objectives 1

1. Clinical activity will be measured by pathological complete response (pCR) and minimal residual disease (MRD), defined as a tumor burden of 5 mm or less in greatest dimensions. The secondary objectives include measures of disease-free survival: PSA-progression free survival up to 1 year after prostatectomy.

Conditions and MedDRA coding

Patients with very high-risk prostate cancer (as defined by a total Gleason-Score ≥4+4 [ISUP-GG 4+5] and clinical stage cT3 (digital rectal examinations or imaging based) plus clinical nodal status cN+ or Serum-PSA level > 20 ng/ml who are candidates for radical prostatectomy with pelvic lymph node dissection.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Must be ≥18 years of age
2. Signed an informed consent form (ICF) indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study; participants must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
3. Histologically confirmed adenocarcinoma of the prostate including following criteria: Very High‐risk defined by a total Gleason‐Score ≥4+4 (ISUP‐GG 4+5) and clinical stage cT3 (digital rectal examination or imaging based) plus clinical nodal status cN+ or Serum‐PSA level >20ng/ml
4. Exclusion of metastases (M0) on conventional imaging and maximum oligometastatic status (maximum 3 bone lesions) on PSMA PET imaging
5. Treatment naïve patients
6. Eastern Cooperative Oncology Group ECOG 0‐1
7. Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
8. Patients must be PSMA Positron Emission Tomography (PET) scan positive with a prostatic SUVmax > 12 (PRIMARY Score: 5) .
9. Following laboratory criteria must be obtained within 14 days prior to randomization:  Bone Marrow reserve • White blood cells, WBC ≥ 2000/μL • Neutrophils ≥ 1500/μL • Platelets ≥ 100 x103/μL • Hemoglobin ≥ 9.0 g/dL  Hepatic • AST/ALT ≤ 3 x ULN • Total Bilirubin ≤ 1.5 x ULN (except participants with Gilbert Syndrome, who may have total bilirubin < 3.0 mg/dL)  Renal • Serum creatinine ≤ 1.5xULN  Endocrine • TSH 0,4 ‐ 4,0 mU/l = 0,4 ‐ 4,0 μU/ml o If TSH is not in normal range, fT3 and fT4 must be determined o fT3 2,3 ‐ 4,5 pg/ml = 3,5 ‐ 7,0 pmol/l o fT4 0,8 ‐ 1,8 ng/dl = 8 ‐ 18 ng/l = 10 ‐ 23 pmol/l  Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L)  Electrolytes: • Potassium: 3.5‐5 mmol/L • Sodium: 135‐145 mmol/L  Pancreatic: • amylase, lipase ≤ 3 x ULN  alkaline phosphatase (range to be assessed in context of oligometastatic disease)  blood sugar < 200 mg/dL (11.1 mmol/L)
10. Sexually active patients must use a condom to prevent them from fathering a child and to prevent delivery of study treatment via seminal fluid to their partner for at least 14 weeks after the last dose of [177Lu]Lu‐PSMA‐617
11. Tumor tissue of both prostate biopsy and radical prostatectomy specimen available for local histology review and reference pathology by Professor Henning Reis (Department of Pathology, University Hospital Frankfurt)

Exclusion criteria 22

1. 1. Distant metastasis (clinical stage M1) on conventional imaging. Oligometastatic (maximum 3 bone lesions ) patients on exclusively PSMA PET imaging will not be excluded. Patients with PSA values below 20ng/ml and no evidence of nodal disease are excluded.
2. Prior treatment with androgen receptor antagonists. Treatment with GnRH analogs prior to ICF signature
3. Bilateral orchiectomy
4. History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
5. Use of any investigational agent ≤4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
6. Major surgery ≤4 weeks prior to randomization
7. Prior therapy with CTLA4 antibodies
8. Previous treatment with any of the following within 6 months of randomization:  Strontium‐89, Samarium‐153, Rhenium‐186, Rhenium‐188, Radium‐223,  Previous PSMA‐targeted radioligand therapy
9. Any immunosuppressive therapy given within the past 30 days prior to study drug administration (excluding physiologic steroid hormone replacement and / or steroid therapy up to a maximum dose of 10 mg prednisone or equivalent per day)
10. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
11. Lack of availability for clinical follow‐up assessments
12. Other potential life‐threatening malignancies within the past five years requiring treatment
13. Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years
14. Patients with serious intercurrent illness, requiring hospitalization
15. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders
16. Patients carrying organ transplants and/or receiving continuous immunosuppressive medication (other than steroid therapy of up to 10 mg prednisone per day)
17. The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition
18. Known hypersensitivity reaction to any of the components of study treatment
19. Known alcohol or drug abuse
20. Participation in another clinical study and use of any investigational or non‐registered product (drug or vaccine) other than the study treatment within the 30 days before registration
21. Significant disease or condition which, in the investigator’s opinion, would exclude the patient from the study
22. Legal incapacity or limited legal capacity

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Feasibility will be defined as the ability to perform prostatectomy in at least 83,33 % of participants of a treatment arm 85 days after start of neoadjuvant treatment with a maximum delay by 3 weeks in the present study.
2. Safety of neoadjuvant treatment with ipilimumab and [177Lu]Lu-PSMA-617 RLT before radical prostatectomy will be characterized according to Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

Secondary endpoints 2

1. Clinical activity is measured by pathologic complete response (pCR) and minimal residual disease (MRD), which is defined as a tumor burden of 5 mm or less in the largest dimensions.
2. Disease-free survival measurements are also performed. Disease-free survival is defined as PSA progression-free survival up to 1 year after prostatectomy.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Essen AöR

Sponsor organisation

Universitaetsklinikum Essen AöR

Address

Hufelandstrasse 55, Holsterhausen Holsterhausen

City

Essen

Postcode

45147

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Essen AöR

Contact name

Professor Dr. Ulrich Krafft

Public contact point

Organisation

Universitaetsklinikum Essen AöR

Contact name

Universitätsklinikum Essen AöR

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 19 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