Neoadjuvant Lu-PSMA Radioligand Therapy and Ipilimumab in Men With Very High-risk Prostate Cancer

NCT06388369 | Terminated Phase 1

• 1 other identifier: CA184-608
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, open-label Phase I/II study of neoadjuvant treatment with \[177Lu\]Lu-PSMA-617 radioligandtherapy (LuPSMA) with or without Ipilimumab in participants with very high-risk prostate cancer who are candidates for Radical Prostatectomy.

Conditions

Very High Risk Prostate Carcinoma

Outcome Measures

Primary Outcomes (2)

• Feasibility to perform prostatectomy on time

  Feasibility will be defined as the ability to perform prostatectomy in at least 75% of the Analysis population 85 days after start of neoadjuvant treatment with a maximum delay by 3 weeks. A treatment arm will be deemed not feasible in the actual study if \>25% of patients of that arm required a delay of surgery \>3 weeks.

  During the intervention/procedure

• Clinical activity: Proportion of participants in the full analysis set who achieve a pCR

  The proportion of participants in the full analysis set who achieve a pathological complete response (pCR). The assessment of pCR will be reviewed by the central pathologist for all randomized patients with Radical Prostatectomy with pelvic lymphadenectomy conducted. The proportion of participants in the full analysis set who achieve a MRD. The assessment of MRD will be reviewed by the central pathologist for all randomized patients with Radical Prostatectomy with pelvic lymphadenectomy conducted.

  After surgery

Secondary Outcomes (2)

• Safety Profile of neoadjuvant treatment before radical prostatectomy

  Start of neoadjuvant treatment up to 1 year after surgery

• Safety Profile of neoadjuvant treatment before radical prostatectomy

  Start of neoadjuvant treatment up to 1 year after surgery

Study Arms (2)

Neoadjuvant Combination Therapy

EXPERIMENTAL

4 cycles of Ipilimumab 3mg/kg + 2 cycles of 7,4 GBq \[177Lu\]Lu-PSMA-617

Radiation: [177Lu]Lu-PSMA-617; Drug: Ipilimumab

Neoadjuvant Mono Therapy

ACTIVE COMPARATOR

2 cycles of 7,4 GBq \[177Lu\]Lu-PSMA-617

Radiation: [177Lu]Lu-PSMA-617

Interventions

[177Lu]Lu-PSMA-617 RADIATION

2 cycles of 7,4 GBq \[177Lu\]Lu-PSMA-617 at 6 weeks intervals

Neoadjuvant Combination Therapy; Neoadjuvant Mono Therapy

Ipilimumab DRUG

4 cycles of Ipilimumab 3mg/kg at 3 weeks intervals

Neoadjuvant Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Must be ≥18 years of age
• 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
• 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
• Treatment naïve patients
• Eastern Cooperative Oncology Group ECOG 0-1
• Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
• Patients must be PSMA Positron Emission Tomography (PET) scan positive with a prostatic SUVmax \> 12 (PRIMARY Score: 5) .
• 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

You may not qualify if:

• Distant metastasis (clinical stage M1) on conventional imaging. Oligometastatic 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.
• Prior treatment with androgen receptor antagonists. Treatment with GnRH analogs prior to ICF signature
• Bilateral orchiectomy
• History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
• Use of any investigational agent ≤4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
• Major surgery ≤4 weeks prior to randomization
• Prior therapy with CTLA4 antibodies
• 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
• 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)
• Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
• Lack of availability for clinical follow-up assessments.
• Other potential life-threatening malignancies within the past five years requiring treatment
• Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years

Sponsors & Collaborators

• University Hospital, Essen: lead
• Advanced Accelerator Applications: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University Hospital Essen, Clinic of Urology

Essen, 45147, Germany

Location

MeSH Terms

Interventions

Ipilimumab

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first patients are enrolled - without randomization - into the Safety Cohort to assess whether the treatment regime under investigation, i.e. Ipilimumab (3mg/kg) + \[177Lu\]Lu-PSMA-617 RLT (7,4 GBq), is appropriately tolerated as per dose escalation algorithm. If it is established that Ipilimumab (3mg/kg) + \[177Lu\]Lu-PSMA-617 RLT (7,4 GBq) is appropriately tolerated, patients will be randomized into the two arms of the Analysis Cohort: * Arm A: Ipilimumab + \[177Lu\]Lu-PSMA-617 RLT * Arm B: \[177Lu\]Lu-PSMA-617 RLT

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: April 29, 2024
• Study Start: August 25, 2025
• Primary Completion: March 9, 2026
• Study Completion: March 9, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

DE (1)