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

NCT04717154 | Completed Phase 2 DMC

• 3 other identifiers: MOURO048 - INSPIRE2020-001240-25CA184-585
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostatic Neoplasms, Castration-Resistant

Keywords

mCRPC; Immune checkpoint inhibitors; Immunotherapy

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (7)

• Safety endpoint: adverse effects

  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)

• Efficacy endpoint: ORR

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

• Efficacy endpoint: BRR

  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)

• Efficacy endpoint: rPFS

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

• Efficacy endpoint: OS

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

Other Outcomes (1)

• Translational endpoint: biomarkers

  Through study completion, an average of 2 years

Study Arms (1)

Treatment arm

EXPERIMENTAL

Combinatory 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.

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

4 courses of 1mg/kg q3w

Also known as: Yervoy, BMS-734016, MDXOIO, MDX-CTLA4

Treatment arm

Nivolumab BIOLOGICAL

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

Also known as: Opdivo, BMS-936558, MDX1106, ONO-4538

Treatment arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6525GA, Netherlands

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Niven Mehra, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 20, 2021
• Study Start: January 19, 2021
• Primary Completion: August 15, 2024
• Study Completion: December 18, 2025
• Last Updated: January 6, 2026

Record last verified: 2024-04

Locations

NL (1)