EVOLUTION: 177Lu-PSMA Therapy Versus 177Lu-PSMA in Combination With Ipilimumab and Nivolumab for Men With mCRPC

NCT05150236 | Unknown Phase 2 DMC

• 1 other identifier: ANZUP 2001
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II study will investigate the activity and safety of radionuclide 177Lu-PSMA therapy versus 177Lu-PSMA in combination with Ipilimumab and Nivolumab in patients with metastatic castrate resistant prostate cancer (mCRPC).

Conditions

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Prostate Cancer; Neoplasms by Site; Neoplasms; Prostatic Disease

Outcome Measures

Primary Outcomes (1)

• PSA progression free survival (PSA-PFS) at 1 year (PCWG3)

  PSA progression is defined as a rise in PSA by ≥ 25% AND ≥ 2 ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later.

  Date of randomisation to the date of first evidence of PSA progression at 53 weeks post randomisation.

Secondary Outcomes (10)

• PSA response rate (PSA-RR)

  Date of randomisation through to study completion, approximately 3 years from start of recruitment. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA response.

• Frequency and severity of adverse events (CTCAE v5.0)

  Date of first dose of study treatment until 100 days after cessation of study treatment.

• Radiological progression free survival (PCWG3/RECIST1.1)

  Date of randomisation to the date of first evidence of progression on imaging (PCWG3 criteria for bone lesions and RECIST 1.1 for soft tissue lesions) assessed every 12 weeks through to study completion, approximately 3 years from start of recruitment.

• PSA progression free survival (PCWG3)

  Date of randomisation through to study completion, approximately 3 years from start of recruitment.

• Overall survival (OS)

  Through to study completion, approximately 3 years from start of recruitment.

Other Outcomes (1)

• Association between Clinical Outcomes and Possible Prognostic/Predictive Biomarkers (tissue and circulating) including PBMCs, ctDNA and CTCs

  Date of randomisation through to study completion, approximately 3 years from start of recruitment.

Study Arms (2)

Combination 177Lu-PSMA-617, Ipilimumab & Nivolumab

EXPERIMENTAL

177Lu-PSMA (7.5GBq) given every 6 weeks up to 6 cycles in combination with concurrent ipilimumab (3mg/kg Q6W x 4 doses) and nivolumab (1mg/kg Q3W x 8 doses) followed by nivolumab monotherapy (480mg Q4W up to 18 doses) or until disease progression or unacceptable toxicity.

Drug: 177Lu-PSMA-617; Drug: Ipilimumab; Drug: Nivolumab

177Lu-PSMA-617

EXPERIMENTAL

177Lu-PSMA (7.5GBq) given every 6 weeks up to 6 cycles or until disease progression or unacceptable toxicity.

Drug: 177Lu-PSMA-617

Interventions

177Lu-PSMA-617 DRUG

Patients will be given 7.5GBq of Lu-PSMA every 6 weeks up to 6 cycles unless there is unacceptable toxicity, commencing following result of 68Ga-PSMA PET within 28 days of registration.

Also known as: 177Lutetium -PSMA 617 also referred to as 177Lu-PSMA

177Lu-PSMA-617; Combination 177Lu-PSMA-617, Ipilimumab & Nivolumab

Ipilimumab DRUG

Patients will be given 3mg/kg of Ipilimumab every 6 weeks up to 4 doses unless there is unacceptable toxicity, concurrently with Lu-PSMA and Nivolumab.

Also known as: YERVOY

Combination 177Lu-PSMA-617, Ipilimumab & Nivolumab

Nivolumab DRUG

Patients will be given 1mg/kg of Nivolumab every 3 weeks up to 8 doses, concurrently with Lu-PSMA and Ipilimumab unless there is unacceptable toxicity. Followed by 480mg nivolumab monotherapy commencing at week 32. Nivolumab monotherapy will be given to patients every 4 weeks up to 18 doses, or until disease progression or unacceptable toxicity.

Also known as: OPDIVO

Combination 177Lu-PSMA-617, Ipilimumab & Nivolumab

Eligibility Criteria

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

You may qualify if:

• Aged 18 years or older, with histologically confirmed adenocarcinoma of the prostate.
• Castration-resistant metastatic prostate cancer (defined as disease progressing despite castration by orchidectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
• Patients must have progressed on prior novel AR targeted agents for treatment of prostate cancer. Progressive disease defined by at least one of the following:
• PSA progression, minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement. The PSA value at screening should be ≥ 5ng/ml
• Soft tissue or visceral disease progression as per RECIST 1.1
• Bone progression: ≥ 2 new lesions on bone scan as per PCWG3
• Target or non-target lesions according to RECIST 1.1 and PCWG3
• Significant PSMA avidity on PET/CT using 68GaPSMA, defined as SUVmax ≥15 at a site of disease, and SUVmax ≥ 10 at other sites of disease ≥10mm (where there is no impact from partial voluming.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate bone marrow, hepatic and renal function documented within 28 days of registration, defined as:
• Haemoglobin ≥90 g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
• Absolute neutrophil count ≥1.5x109/L
• Platelets ≥100 x109/L
• Total bilirubin ≤1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome
• Aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤2.5 × ULN or ≤5 × ULN for participants with liver metastases

You may not qualify if:

• Prostate cancer with known significant sarcomatoid, spindle cell or neuroendocrine cell components, or metastasis of other cancers to the prostate.
• F-FDG-PET/CT SUVmax ≥10 at a site of measurable disease with no concurrent PSMA expression \> 10mm
• Prior treatment with anti-PD1, anti-PD-L1/L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways.
• Patients must not have had more than one line of chemotherapy. If a patient has had docetaxel chemotherapy for hormone sensitive or castrate resistant setting, this will be considered one line.
• Prior treatment with 177Lu-PSMA.
• Patients with active, known, or suspected autoimmune disease. Sjogren's syndrome is considered an autoimmune disease. Exceptions: Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger, may be eligible.
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids, and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Participants must have recovered from all AE due to previous therapies to ≤Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
• Active malignancies within the previous 2-years with \>30% probability of recurrence within 1 year. Melanoma in situ, basal cell or squamous cell carcinomas of skin, are permitted.
• Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated.
• Radiation or surgery within 2 weeks of randomisation.
• Previous history of interstitial lung disease or non-infectious pneumonitis.
• Administration of a live vaccine within 30 days prior to the first dose of study drug.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Inadequate contraception. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

Sponsors & Collaborators

• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: lead
• Prostate Cancer Foundation of Australia: collaborator
• Bristol-Myers Squibb: collaborator
• Advanced Accelerator Applications: collaborator
• University of Sydney: collaborator

Study Sites (8)

St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Royal Brisbane and Womens hospital

Herston, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Sir Charles Gairdner

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

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

Interventions

Pluvicto; Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

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

Study Officials

• Shahneen Sandhu, MBBS, FRACP

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: December 9, 2021
• Study Start: April 29, 2022
• Primary Completion: August 31, 2024
• Study Completion: December 1, 2024
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Study protocol will be published in a peer-reviewed journal within 24 months.

Locations

AU (8)