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Prostatic Neoplasms, Castration-ResistantPhase 2INSPIRENCT04717154

Ipilimumab With Nivolumab for Molecular-selected Patients With Castration-resistant Prostate Cancer

A Phase 2 study testing Ipilimumab and Nivolumab in people with Prostatic Neoplasms, Castration-Resistant, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the effects of 4 cycles of combinatory immunotherapy (ipilimumab and nivolumab), followed by monotherapy nivolumab in participants with immunogenic metastatic castration-resistant prostate cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Ipilimumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
1 siteNetherlands
Study dates
19 Jan 2021to 18 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible to participate in this study, a subject must meet all of the following criteria:
  • Written informed consent.
  • Histological diagnosis of adenocarcinoma of the prostate. Patients who have no histological diagnosis must be willing to undergo a biopsy to prove prostate adenocarcinoma.
  • Metastatic Castration-Resistant Prostate Cancer (mCRPC), metastatic disease defined either as measurable disease by RECIST1.1 criteria or presence of bone-metastatic disease evaluable per PCWG3 criteria. For cohort 1, measurable disease is compulsory.
  • An immunogenic phenotype, consisting of one of the next criteria: 1, mismatch repair deficiency and/or a high mutational burden of >7 mutations per Mb (cluster A); 2, BRCA2 inactivation or BRCAness signature (cluster B); 3, a tandem duplication signature and/or CDK12 biallelic inactivation (cluster C)
  • Age ≥18 years.
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  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • PSA ≥ 2 ng/ml.
  • Documented willingness to use an effective means of contraception while participating in the study and for 7 months post last dose of treatment
  • Documented ongoing castrate serum testosterone <50 ng/dL (<2.0 nM).
  • Received prior castration by orchiectomy and/or ongoing Luteinizing Hormone-Releasing Hormone (LH-RH) agonist treatment.
  • Progression of disease by:
  • PSA utilizing PCWG3 criteria
  • Bone scan: disease progression as defined by at least 2 new lesions on bone scan.
  • Soft tissue disease progression defined by modified RECIST 1.1.
  • Clinical progression with worsening pain and the need for palliative radiotherapy for bone metastases.
  • Having a biopsiable metastatic lesion and willingness to undergo a baseline* and on treatment tumour biopsy for next-generation sequencing and biomarker analyses.
  • When sufficient FFPE material is available from a biopsy in castrate-state, one may apply for a waiver for a new baseline biopsy.

Who cannot join

  • A potential subject who meets any of the following criteria will be excluded from participation in this study:
  • Prior treatment with checkpoint immunotherapy (CTLA-4, or PD-1 and PD-L1 antagonists) for cohort 1. For cohort 2, patients may have prior treatment with monotherapy CTLA-4 or PD-1 or PD-L1.
  • Surgery or chemotherapy within 4 weeks prior to trial entry / randomisation into the study. Any other therapies for prostate cancer, other than GnRH analogue therapy and osteoporosis preventing agents, are not allowed.
  • Radiotherapy within 2 weeks prior to trial entry. Radiation-related side effects higher than grade 1, or above baseline.
  • Participation in another interventional clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry/randomisation.
  • History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumours, brain metastases, or alcoholism.
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  • Untreated or symptomatic brain or leptomeningeal involvement.
  • Inadequate organ and bone marrow function as evidenced by:
  • hemoglobin <6.2 mmol/L
  • Absolute neutrophil count <1.0 x 109/L
  • Platelet count < 75 x 109/L
  • Albumin <30 g/dL.
  • AST / SGOT and/or ALT / SGPT ≥ 2.5 x ULN (≥ 5 x ULN if liver metastases present)
  • Total bilirubin ≥ 1.5 x ULN (except for patient with documented Gilbert's disease)
  • Serum Creatinine > 1.5 x ULN
  • Any of the following cardiac criteria; a. Any clinically significant abnormalities in rhythm conduction, or morphology of a resting ECG (e.g., complete left bundle branch block, third degree heart block) c. Experience of any of the following procedures or conditions in the preceding six months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, congestive heart failure NYHA ≥ Grade2 d. Uncontrolled hypotension defined as systolic blood pressure (BP) <90mmHg and/or diastolic BP <50mmHg
  • Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
  • History of clinically relevant auto-immune disease (including Crohn's disease or ulcerative colitis). Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of nivolumab or ipilimumab or that may affect the interpretation of the results or renders the patients at high risk from treatment complications.
  • Need for chronic corticosteroid therapy of >10 mg of prednisolone or >0.5mg of dexamethasone per day or an equivalent dose of other anti-inflammatory corticosteroid. Patients in which corticosteroids cannot be stopped prior to entering the trial are allowed a maximum of 10mg of prednisolone per day or equivalent. In the case of corticosteroid discontinuation, a 2-week (14 days) washout is required with a mandatory PSA check prior to starting the trial. If the PSA has declined compared to the value obtained prior to stopping corticosteroids, patients will not be eligible for study. Patients can only enter the study with a confirmed PSA increase.
  • Malignancies other than prostate cancer within 3 years prior to trial entry / randomization, except for adequately treated basal or squamous cell skin cancer and non-muscle invasive bladder cancer.
  • Active second malignancy, except basal or squamous cell skin cancer and non-muscle invasive bladder cancer. Other treated malignancies with curative intent, including colorectal cancer, may be included following PI consent.
  • Unresolved clinically significant toxicity from prior therapy except for alopecia and Grade 1 peripheral neuropathy.
  • Inability to comply with study and follow-up procedures.
  • Patients with predominant small cell or neuroendocrine prostate cancer are not eligible.
  • Patients without measurable lesion per RECIST1.1, and with a superscan on bone scintigraphy not evaluable per PCWG3 criteria, are not eligible

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Radboudumc

    Nijmegen, Gelderland, 6525GA

Other trials in Netherlands

About this study

Official title: Phase 2 INSPIRE Trial: Ipilimumab With Nivolumab for Molecular- Selected Patients With Castration-resistant Prostate Cancer

The purpose of this study is to evaluate the effects of 4 cycles of combinatory immunotherapy (ipilimumab and nivolumab), followed by monotherapy nivolumab in participants with immunogenic metastatic castration-resistant prostate cancer.

Read the detailed description

Following molecular characterization (next-generation sequencing) a total of 75 mCRPC patients with a putative immunogenic subtype will be included within the phase 2 INSPIRE trial. As treatment we will be utilizing a combinatory regimen of nivolumab 3mg/kg and ipilimumab 1mg/kg for 4 doses, followed by nivolumab 480mg flat dose for up to one year. All participants will additionally undergo an on-trial metastatic tissue biopsy. Translational research will study immunological correlates and in-depth genomic/transcriptomic and multispectral immunohistochemical analyses of immune infiltrate.

Being tested
Ipilimumab, Nivolumab
Keywords
mCRPC, Immune checkpoint inhibitors, Immunotherapy
Medical subject headings
Prostatic Neoplasms, Castration-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Yervoy, BMS-734016, MDXOIO, MDX-CTLA4

    4 courses of 1mg/kg q3w

  • NivolumabBiological

    Also called Opdivo, BMS-936558, MDX1106, ONO-4538

    4 courses of 3mg/kg q3w, followed by maintenance flat dose (480mg, q4w, for 10 doses)

Study groups in NCT04717154
Study groupRoleWhat they receive
Treatment armExperimentalCombinatory regimen of nivolumab 3mg/kg and ipilimumab 1mg/kg, followed by nivolumab 480mg flat dose (Q4w) to up to one year. This regimen will be given to participants in both cohort 1 and 2.
Receives: Biological: Ipilimumab; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy endpoint: DCR

    For patients with RECIST1.1 evaluable disease this includes a change from baseline in tumour volume as measured by PR or CR by best ORR, or an SD, all lasting longer than 6mo, and the absence of clinical disease progression.

    In patients without RECIST1.1 evaluable disease, disease control is defined by the absence of new measurable lesions and unequivocal PD of non-target lesions on CT scan, the absence of bone progression as defined by the PCWG3 criteria, and the absence of clinical disease progression

    Measured: At inclusion, Weeks 7, 17, 29, and 41, and 30 days after last dose given at week 49

Secondary outcomes (7)

  1. Safety endpoint: adverse effects

    Percentage of Grade 3/4 and 5 treatment-related adverse effects

    Measured: At inclusion, Weeks 1, 4, 7, 10, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and at end of treatment (typically at one year, or earlier when treatment is stopped prematurely)

  2. Efficacy endpoint: ORR

    Best objective response rate (ORR) per RECIST1.1 criteria (cohort A1 only)

    Measured: At inclusion, Weeks 7, 17, 29, and 41, and 30 days after last dose given at week 49

  3. Efficacy endpoint: BRR

    Biochemical response rate (BRR) at week 13 and maximal PSA decline according to PCWG3 criteria

    Measured: BRR at Week 13, PSA at inclusion, Weeks 1, 4, 7, 10, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and at end of treatment (typically one year, or earlier when treatment is stopped prematurely)

  4. Efficacy endpoint: rPFS

    Radiographic progression free survival per irRECIST1.1 immune-related response criteria

    Measured: At inclusion, Weeks 7, 17, 29, and 41, and 30 days after last dose given at week 49

  5. Efficacy endpoint: OS

    Overall survival

    Measured: Follow-up of 1 year following trial discontinuation (onwards from the 30-day safety follow-up visit).

  6. Efficacy in the BRCA, CDK12 and MSI/hTMB subgroups

    DCR, ORR, BRR, rPFS and OS per subgroup

    Measured: At inclusion, Weeks 7, 17, 29, and 41, and 30 days after last dose given at week 49

  7. Efficacy in the subgroup of patients with prior RT

    DCR, ORR, BRR, rPFS and OS in patients with and without prior radiotherapy

    Measured: At inclusion, Weeks 7, 17, 29, and 41, and 30 days after last dose given at week 49

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2021
  2. Study start19 Jan 2021
  3. Primary completion15 Aug 2024
  4. Study completion18 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open label, single treatment, phase II study: * Cohort A1 will assess the efficacy of ipilimumab+nivolumab in mCRPC patients with RECIST1.1 measurable disease that are naïve for immune checkpoint inhibition * Cohort A2 will assess the efficacy of ipilimumab+nivolumab in patients without RECIST1.1 measurable disease that are naïve for immune checkpoint inhibition * Cohort B will assess the efficacy of ipilimumab+nivolumab in patients with RECIST1.1 measurable disease and prior progression to immune checkpoint inhibitor monotherapy (CTLA-4 or anti-PD1/PDL1)
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04717154
Sponsor's protocol ID
MOURO048 - INSPIRE
Other IDs
2020-001240-25, CA184-585
Acronym
INSPIRE
Status last verified
Apr 2024
First submitted
6 Jan 2021
Last updated
6 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab and Nivolumab in people with Prostatic Neoplasms, Castration-Resistant, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy endpoint: DCR (time frame: At inclusion, Weeks 7, 17, 29, and 41, and 30 days after last dose given at week 49). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04717154.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.

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