Durvalumab and Olaparib for the Treatment of Prostate Cancer in Men Predicted to Have a High Neoantigen Load

NCT04336943 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1007001NCI-2020-0186010509
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well durvalumab and olaparib work in treating prostate cancer in men predicted to have specific genetic mutations (a high neoantigen load). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving durvalumab and olaparib may kill more tumor cells in patients with prostate cancer predicted to have a high neoantigen load.

Conditions

Biochemically Recurrent Prostate Carcinoma; Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Undetectable Prostate Specific Antigen (PSA)

  Will assess if patients achieve undetectable PSA for post-prostatectomy patients (including those that also received salvage radiation) or PSA \< 0.5 ng/ml for post-definitive radiation patients.

  At 12 months after initiation of therapy

Secondary Outcomes (3)

• PSA50 Response

  At 3 and 6 months

• Change in Quality of Life: RANDSF-36

  At the time of enrollment and then every three months, with the last assessment at 12 months.

• Change in Quality of Life: IIEF

  At the time of enrollment and then every three months, with the final measurement after 12 months.

Study Arms (1)

Treatment (durvalumab, olaparib)

EXPERIMENTAL

All patients receive durvalumab IV over 1 hour on day 1 of each cycle. Patients with CDK12 mutation and MMRd/MSI-high also receive olaparib PO BID on days 1- 28 of cycles 3-6. Patients with homologous recombination mutation also receive olaparib PO BID on days 1-28 of cycles 1-6. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Drug: Olaparib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736, 1428935-60-7

Treatment (durvalumab, olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (durvalumab, olaparib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (durvalumab, olaparib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (durvalumab, olaparib)

Eligibility Criteria

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

You may qualify if:

• Histologic confirmation of adenocarcinoma of the prostate
• PSA must be \>= 2 ng/ml if received only prior definitive radiation (no PSA threshold required if prior prostatectomy was performed) with a PSA doubling time (PSADT) =\< 10 months:
• PSADT calculation must include all recorded PSA values \> 0.2 ng/ml over the past 6 months prior to randomization, with a minimum of 3 values spaced at least 2 weeks apart, with each included value preferably measured at the same laboratory. PSA values obtained prior to localized therapy will be excluded
• The calculation of PSADT is based on the natural log of PSA
• Prior salvage radiation or not a candidate for localized salvage radiation due to subject preference or clinical assessment based upon disease characteristics and/or subject co-morbidities
• Prior hormonal therapy (i.e. androgen deprivation therapy) when given as neoadjuvant/concurrent/adjuvant therapy along with definitive radiation is allowed, provided this was stopped \>= 6 months prior to starting treatment per protocol AND testosterone is \>= 150 ng/dl
• No evidence of metastatic disease on imaging by whole body bone scan and computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 6 weeks before study therapy start day. PSMA positron emission tomography (PET) or fluciclovine scan within 6 weeks of start day may substitute other imaging studies.
• Patients with oligometastatic disease (i.e. =\< 3 sites) detectable on advanced imaging only (e.g. PSMA or fluciclovine PET) are eligible
• Abdominal or pelvic lymph nodes measuring =\< 2 cm in short axis are allowed
• Biomarker positive:
• Biallelic CDK12 inactivating mutations as documented using a clinical grade sequencing assay performed in a Clinical Laboratory Improvement Act (CLIA)/College of American Pathologists (CAP) certified laboratory or
• MMRd/MSI-high as documented using a clinical grade assay performed in a CLIA/CAP certified laboratory or
• Loss of function mutations in homologous recombination genes (i.e. homologous recombination deficiency; HRD) as documented using a clinical grade sequencing assay performed in a CLIA/CAP certified laboratory. Homologous recombination genes include, but not limited to BRCA1, BRCA2, ATM, CHEK2, PALB2, RAD51D, NBN, GEN1, RAD51C, MRE11A, BRIP11A, FAM175A.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Age \> 18 years at time of study entry.

You may not qualify if:

• Prior chemotherapy for prostate cancer, unless done in the neoadjuvant setting, and if the last dose was \> 6 months prior to enrollment
• Any prior treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• Any prior treatment with a PARP inhibitor, including olaparib
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease \>= 3 years before the first dose of durvalumab and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis
• Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the treating physician (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fridericia \[QTcF\] prolongation \> 470 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
• Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the study physician
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, extensive bilateral lung disease on high resolution computed tomography (HRCT) scan, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea or any psychiatric disorder that prohibits obtaining informed consent
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Immunocompromised patients, e.g., patients with uncontrolled human immunodeficiency virus (HIV). HIV+ patients will be allowed on the study if on highly active antiretroviral therapy (HAART) and disease is controlled: CD4 \>= 350 cell/mcl, undetectable viral load, and no prophylactic (PPX) antibiotics

Sponsors & Collaborators

• University of Washington: lead
• AstraZeneca: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

durvalumab; Immunoglobulin G; Disulfides; olaparib

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Dr. Michael Schweizer
• Organization: Fred Hutchinson Cancer Center

mtschwei@fredhutch.org

2066066252

Study Officials

• Michael Schweizer

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 7, 2020
• Study Start: April 13, 2021
• Primary Completion: June 20, 2024
• Study Completion: June 6, 2025
• Last Updated: August 11, 2025
• Results First Posted: August 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)