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

NCT07090369 | Not Yet Recruiting Phase 1

• 1 other identifier: 24/186
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Keywords

prostate cancer; olaparib; pembrolizumab; 177Lu-PSMA; metastatic castrate resistant prostate cancer; triplet therapy

Outcome Measures

Primary Outcomes (2)

• 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

  24 months from recruitment of last patient

• 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.

  24 months from recruitment of last patient

Secondary Outcomes (5)

• PSA50 response rate

  24 months from recruitment of last patient

• PSA90 response rate

  24 months from recruitment of last patient

• PSA progression free survival

  24 months from recruitment of last patient

• Overall Survival

  24 months from recruitment of last patient

• Objective Response Rates

  24 months from recruitment of last patient

Study Arms (1)

177Lu-PSMA + olaparib + pembrolizumab

EXPERIMENTAL

Patients 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.

Drug: Olaparib (300 mg BID); Drug: Pembrolizumab; Radiation: 177Lu-PSMA-I&T

Interventions

Olaparib (300 mg BID) DRUG

oral tablet

177Lu-PSMA + olaparib + pembrolizumab

Pembrolizumab DRUG

IV infusion

177Lu-PSMA + olaparib + pembrolizumab

177Lu-PSMA-I&T RADIATION

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

177Lu-PSMA + olaparib + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; BID protein, human; pembrolizumab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Shahneen Sandhu

CONTACT

+61 3 8559 7902; Shahneen.Sandhu@petermac.org

Ramin Alipour, ramin.alipour@petermac.org

CONTACT

+61 3 8559 7000; ramin.alipour@petermac.org

Study Design

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

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: July 29, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 29, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)