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Metastatic Castrate Resistant Prostate Cancer (mCRPC)Phase 1LumOnateNCT07090369

Phase Ib Trial of 177Lu-PSMA-I&T Therapy in Combination With Olaparib and Pembrolizumab in Patients With Metastatic Castration Resistant Prostate Cancer

A Phase 1 study testing Olaparib (300 mg BID), Pembrolizumab and 177Lu-PSMA-I&T in people with Metastatic Castrate Resistant Prostate Cancer (mCRPC), run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase 1b trial is designed to evaluate the safety and tolerability of olaparib in combination with 177Lutetium-Prostate Specific Membrane Antigen (177 Lu-PSMA) and pembrolizumab in patients with metastatic castration resistant prostate cancer (mCRPC). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Olaparib (300 mg BID), Pembrolizumab and 177Lu-PSMA-I&T
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteAustralia
Study dates
1 Nov 2025to 1 Dec 2028
Phase
Phase 1
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

  • Patient must have provided written informed consent using the LumOnate Patient Information and Consent Form (PICF)
  • Patient must be ≥ 18 years of age at Screening
  • Willing and able to comply with treatment schedule, laboratory testing, and other requirements of the study
  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • At least 2 weeks since the completion of prior therapy, including surgery or radiotherapy
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  • PSA > 5 ng/mL
  • Significant PSMA avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease, and SUVmax > 10 at other sites of disease ≥ 10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
  • Radiographic evidence of metastatic disease documented with either bone scan or CT scan (Appendix 2)
  • Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
  • Haemoglobin ≥ 100 g/L independent of transfusions (no red blood cell transfusion in last 8 weeks)
  • Absolute neutrophil count ≥ 1.5 x 109/L
  • Platelets ≥ 150 x 109/L
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
  • Albumin ≥ 30 g/L
  • Adequate renal function: Patients must have creatinine clearance (CrCl) estimated of ≥ 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test
  • Patients must have progressed on an ARPI (e.g. enzalutamide, abiraterone, darolutamide/or apalutamide). Determination of disease progression on an ARPI will be made by the local Investigator
  • Patients must have progressive disease defined as any 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 ≥ 5 ng/mL
  • Soft tissue or visceral disease progression as per modified RECIST 1.1 criteria (Appendix 2)
  • Bone progression: ≥ 2 new lesions on bone scan (Appendix 2)
  • Prior surgical orchiectomy or chemical castration maintained on ongoing luteinizing hormone-releasing hormone analogue (agonist or
  • Patients must have a life expectancy ≥ 24 weeks
  • Non-sterilised male patients who are sexually active with a female partner of childbearing potential must use a condom from screening to approximately 3 months after the last dose of treatment. Female partners of male patients should also use a highly effective form of contraception throughout this period
  • Patients who are deemed to have disease that is safe and amenable to biopsy based on screening PSMA PET scans will be mandated to consent to paired tumour biopsies at Screening and on treatment

Who cannot join

  • Prior chemotherapy for mCRPC. Prior docetaxel is permitted if given in the setting of hormone sensitive disease
  • Site(s) of disease that are FDG positive with low PSMA expression defined by PSMA SUVmax < 10
  • Extensive marrow disease defined by a "Super Scan" on bone scintigraphy or diffuse marrow infiltration on PSMA PET
  • Active brain metastases or leptomeningeal metastases
  • Any prior exposure to anti-PD-1, anti-PD-L1/L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway
  • Any prior exposure to PARP inhibitors, platinum, or radionuclide therapy
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  • Patients with a history or clinical features suggestive of myelodysplastic syndrome/acute myeloid leukaemia or previously known clonal haemopoiesis
  • Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan or psychiatric illness/social situations that is likely to impede participation and /or compliance in the study
  • Patients with active, known, or suspected autoimmune disease Note: Patients with vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol
  • Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of registration Note: Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone are permitted in the absence of active autoimmune disease
  • Malignancy within the previous 2 years other than basal cell or squamous cell carcinomas, skin or melanoma in situ, or other cancers that are unlikely to recur within 24 months
  • Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C ribonucleic acid (HCV PCR) indicating acute or chronic infection
  • Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable
  • Persistent toxicities (CTCAE ≥ Grade 2) caused by previous cancer therapy, excluding alopecia
  • Previous history of interstitial lung disease or non-infectious pneumonitis
  • Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the Investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
  • Known hypersensitivity to olaparib or pembrolizumab or any of the excipients of olaparib or pembrolizumab
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) 1/2. Only need to check this if there is a clinical history. HIV-infected (HIV1/2 antibody-positive) patients may participate if they meet all the following eligibility requirements:
  • They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within 12 weeks prior to registration
  • They must have a CD4 count ≥ 250 cells/µL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/µL over the past 2 years unless it was deemed related to the cancer and/or chemotherapyinduced bone marrow suppression
  • For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/µL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
  • They must have an undetectable viral load and a CD4 count ≥ 250 cells/µL within 7 days prior to registration
  • They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within 6 months prior to registration
  • Concomitant use of known strong cytochrome P450, family 3 (CYP3A) inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks
  • Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and enzalutamide, and 3 weeks for other agents
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
  • Participation in another clinical study with an investigational product or another systemic therapy administered within 3 weeks prior to registration

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

Other trials in Australia

About this study

This phase 1b trial is designed to evaluate the safety and tolerability of olaparib in combination with 177Lutetium-Prostate Specific Membrane Antigen (177 Lu-PSMA) and pembrolizumab in patients with metastatic castration resistant prostate cancer (mCRPC).

Read the detailed description

This phase 1b, multi-centre, single arm, open label study is designed to evaluate the safety and tolerability of olaparib in combination with 177Lu-PSMA with concurrent treatment with pembrolizumab in patients with mCRPC. Patients with mCRPC who have previously progressed an Androgen Receptor Pathway Inhibitor (e.g. enzalutamide, abiraterone, darolutamide/or apalutamide) and have not had prior exposure to anti-PD-1, anti-PD-L1/L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway, platinums, PARP inhibitors or radionuclide therapy will be eligible for the study. Patients can have had prior exposure to docetaxel in the chemotherapy naïve setting or castrate setting.

This is a single arm study divided into two treatment parts. In Part 1, patients will receive olaparib (oral; day 1-22),177Lu-PSMA (IV infusion; day 5), and pembrolizumab (IV infusion; day 1 and 22) for a maximum of six cycles (cycle = 42 days) of treatment. In Part 2, patients will continue to be treated with single agent pembrolizumab (IV infusion; day 1 and 22) for a subsequent 12 cycles (cycle = 42 days) of treatment.

Patients will be followed up every six weeks after the last dose of treatment until disease progression by modified RECIST 1.1 and/or PCWG3, start of new anti-prostate cancer therapy, withdrawal of consent, death, or 2 years a er the last patient has commenced treatment, whichever is earlier.

Being tested
Olaparib (300 mg BID), Pembrolizumab, 177Lu-PSMA-I&T
Keywords
prostate cancer, olaparib, pembrolizumab, 177Lu-PSMA, metastatic castrate resistant prostate cancer, triplet therapy
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • Olaparib (300 mg BID)Drug

    oral tablet

  • PembrolizumabDrug

    IV infusion

  • 177Lu-PSMA-I&TRadiation

    PSMA-I\&T is a small molecule ligand that binds to the extra-cellular domain of the prostatespecific membrane antigen. PSMA-I\&T is a small molecule ligand that binds to the extra-cellular domain of the prostatespecific membrane antigen

Study groups in NCT07090369
Study groupRoleWhat they receive
177Lu-PSMA + olaparib + pembrolizumabExperimentalPatients will receive treatment in two parts. A cycle in both parts is 42 days. In part 1, patients will receive a combination of olaparib (oral; days 1-22), a fixed 7.4 GBq dose of 177Lu-PSMA (IV infusion; day 5) and pembrolizumab (IV infusion; days 1 and 22). In part 2, patients will be administered with single agent pembrolizumab (IV infusion; days 1 and 22) for an additional 12 cycles of treatment.
Receives: Drug: Olaparib (300 mg BID); Drug: Pembrolizumab; Radiation: 177Lu-PSMA-I&T

What is being measured

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

  1. Progression Free Survival

    To describe the radiological progression free survival (modified RECIST 1.1 and/or PCWG3 criteria) of the combination of 177Lu-PSMA-I\&T, olaparib and pembrolizumab

    Measured: 24 months from recruitment of last patient

  2. Safety of Combination Therapy

    To evaluate the safety of 177Lu-PSMA-I\&T in combination with olaparib and pembrolizumab. All adverse events (AE's) will be reported using CTCAE 5.0, with the severity (grade) and causality (relationship to investigational products) recorded for each participant.

    Measured: 24 months from recruitment of last patient

Secondary outcomes (5)

  1. PSA50 response rate

    To evaluate the PSA50 response rate

    Measured: 24 months from recruitment of last patient

  2. PSA90 response rate

    To evaluate the PSA90 response rate

    Measured: 24 months from recruitment of last patient

  3. PSA progression free survival

    To evaluate PSA progression free survival

    Measured: 24 months from recruitment of last patient

  4. Overall Survival

    To evaluate the overall survival

    Measured: 24 months from recruitment of last patient

  5. Objective Response Rates

    To evaluate objective response rates in patients with measurable disease by modified RECIST 1.1

    Measured: 24 months from recruitment of last patient

Timeline

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

  1. First posted29 Jul 2025
  2. Study start1 Nov 2025 (estimated)
  3. Primary completion1 Dec 2028 (estimated)
  4. Study completion1 Dec 2028 (estimated)

Why it stopped: Funding issues

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07090369
Sponsor's protocol ID
24/186
Acronym
LumOnate
Status last verified
Oct 2026
First submitted
15 Jul 2025
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Olaparib (300 mg BID), Pembrolizumab and 177Lu-PSMA-I&T in people with Metastatic Castrate Resistant Prostate Cancer (mCRPC), run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

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 26 inclusion and 28 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: withdrawn, as of the sponsor's last update on 30 Oct 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 Australia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 was withdrawn before enrolling participants, so there are no results.

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?

Progression Free Survival (time frame: 24 months from recruitment of last patient). The study lists 2 primary outcomes in all. 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 NCT07090369.

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 30 Oct 2026.

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