Durvalumab + Olaparib for Prostate Cancer

Palo Alto (17 mi)

Overseen byMichael Schweizer

Age: 18+

Sex: Male

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: University of Washington

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

Men with prostate cancer who've had local therapy, a rising PSA level, and no metastatic disease on scans. They must have specific genetic mutations indicating a high neoantigen load, not received certain prior treatments like chemotherapy or immunotherapy, and can't be immunocompromised. Participants need to be over 18 years old with an ECOG performance status of =<1 (able to carry out light activity), adequate organ function, and willing to use contraception.

Inclusion Criteria

My PSA is at least 2 ng/ml after radiation, or I've had a prostatectomy. My PSA doubles in 10 months or less.

I will use a condom during and for 3 months after treatment if my partner could become pregnant.

My kidneys are functioning well, with a creatinine clearance rate of at least 51 mL/min.

My cancer has specific genetic changes.

I stopped hormonal therapy over 6 months ago and my testosterone is above 150 ng/dl.

My body weight is over 30 kg.

I have had surgery or radiation for prostate cancer.

My prostate cancer is confirmed to be adenocarcinoma.

My cancer has spread to 3 or fewer places, as shown by advanced scans.

I can carry out all my self-care activities without assistance.

My hemoglobin level is at least 10.0 g/dL without recent blood transfusions.

Exclusion Criteria

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I have never been treated with a PARP inhibitor like olaparib.

I do not have any serious, uncontrolled health issues or infections.

I am not taking strong or moderate CYP3A inhibitors.

I have had cancer spread to the lining of my brain and spinal cord.

I have had a bone marrow or cord blood transplant in the past.

I had major surgery more than 2 weeks ago and have recovered.

My heart condition is stable and does not include uncontrolled issues or long QT syndrome.

I cannot swallow pills or have stomach issues affecting medication absorption.

I do not have an active infection like TB or hepatitis.

I am not taking any strong or moderate drugs that affect liver enzymes.

I haven't had extensive radiation to my bone marrow or wide field radiation in the last 4 weeks.

I have previously been treated with a PD1 or PD-L1 inhibitor.

I have not received a live vaccine within the last 30 days.

Treatment Details

The trial is testing the combination of durvalumab (an immune system-boosting monoclonal antibody) and olaparib (a PARP inhibitor that prevents cancer cells from repairing their DNA) in men whose prostate cancer has specific genetic features suggesting they might respond well to these drugs.

1Treatment groups

Experimental Treatment

Group I: Treatment (durvalumab, olaparib)Experimental Treatment4 Interventions

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.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺 Approved in European Union as Imfinzi for: