What is the mechanism of action of this treatment?

Common treatments for prostate cancer, such as Nivolumab and Vidutolimod, work by harnessing the body's immune system to target and destroy cancer cells. Nivolumab is a PD-1 inhibitor that prevents the immune system from being shut down by cancer cells, allowing immune cells to attack the tumor. Vidutolimod, a TLR9 agonist, stimulates the immune system to produce tumor-targeted T cells, enhancing the immune response. These treatments are significant for prostate cancer patients as they offer new avenues for combating cancer, particularly in cases where the disease has become resistant to conventional therapies.

What side effects are associated with this type of intervention?

Common side effects of immune checkpoint inhibitors like Nivolumab (PD-1 Inhibitor) include fatigue, rash, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. TLR9 agonists, such as Vidutolimod, may cause flu-like symptoms, injection site reactions, and potentially enhance immune-related adverse events when combined with checkpoint inhibitors. Patients should be closely monitored for these side effects to manage them promptly.

What prior FDA approvals exist?

FDA-approved treatments for prostate cancer include androgen deprivation therapies, chemotherapy agents like Docetaxel, and hormonal agents such as Enzalutamide and Abiraterone. Sipuleucel-T, an autologous cellular immunotherapy, is also approved for metastatic castration-resistant prostate cancer. While PD-1 inhibitors like Nivolumab are approved for various cancers, they are not specifically approved for prostate cancer. There is limited information on the approval of TLR9 agonists for prostate cancer.

What other types of research exist?

Promising alternatives to Vidutolimod and Nivolumab for prostate cancer treatment in 2024 include: 1) Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, which has shown efficacy in urothelial carcinoma and is being explored in other cancers. 2) Relatlimab, a LAG-3 inhibitor, which in combination with Nivolumab has shown promise in melanoma and may be applicable to prostate cancer. 3) PSMA-targeted therapies, such as PSMA-617 linked to Lutetium-177, which have shown significant efficacy in prostate cancer. These alternatives represent novel mechanisms of action and have the potential to improve outcomes for prostate cancer patients.

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Checkpoint Inhibitor

Vidutolimod + Nivolumab for Prostate Cancer

Phase 2

Waitlist Available

Led By Mehmet A Bilen, M.D.

Research Sponsored by Emory University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects refractory to a novel antiandrogen therapy and failed at least 1 taxane based chemotherapy regimen

Willingness to provide pre- and post-treatment fresh tumor biopsies

Must not have

Adverse event related to previously administered anti-cancer therapy not resolved to < grade 2 prior to the first dose of CMP-001

History of immune-related adverse event requiring permanent discontinuation of anti-PD1/PDL1 antibody

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 1 year

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests whether combining vidutolimod and nivolumab can help treat prostate cancer that has spread and is resistant to hormone therapy. Vidutolimod activates immune cells, and nivolumab helps these cells recognize and attack cancer. The goal is to see if this combination can safely and effectively kill more cancer cells.

Who is the study for?

Men over 18 with advanced prostate cancer resistant to certain therapies and chemotherapy, or those unsuitable for such treatments. Participants must have stable vital functions, no severe bleeding risks, measurable disease amenable to injection, and be willing to provide biopsies. They should not have other active cancers or serious illnesses that could interfere with the trial.

What is being tested?

The trial is testing vidutolimod combined with nivolumab in men whose prostate cancer has spread despite treatment. Vidutolimod activates immune cells while nivolumab blocks a protein that turns off the immune response, potentially allowing the body to better fight cancer.

What are the potential side effects?

Possible side effects include reactions at the injection site, flu-like symptoms from vidutolimod (fever, chills), and typical immunotherapy-related issues like fatigue, skin rash or inflammation of organs due to nivolumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have cancer that didn't respond to a new hormone therapy and one chemotherapy.

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I am willing to provide tissue samples before and after treatment.

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My prostate cancer has spread to other parts of my body.

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I have had an orchiectomy or my testosterone levels are below 50 ng/dL.

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My kidney function, measured by creatinine levels, is within the normal range.

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I am a man who is either surgically sterile or will use contraception.

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My blood clotting tests are normal or near normal, unless I'm on blood thinners.

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I am a man aged 18 or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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All my side effects from previous cancer treatments are mild.

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I stopped taking anti-PD1/PDL1 due to a severe side effect.

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I am currently on medication for an infection.

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My prostate cancer is not adenocarcinoma but a different type.

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I have not had a live virus vaccine in the last 30 days.

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I haven't had cancer treatment in the last 14 days.

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I have untreated brain metastases that are causing symptoms or getting bigger.

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I have had a transplant of tissue or an organ from another person.

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I have had pneumonitis treated with steroids or have it now.

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I have another cancer that is getting worse or needed treatment in the last 3 years.

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I have been treated with CMP-001 or anti-PD1/PDL1 before.

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I have taken more than 10 mg/day of prednisone or similar medication in the last week.

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I have been diagnosed with HIV, hepatitis B, or hepatitis C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety of Treatment

Secondary study objectives

ORR

Objective response rate (ORR)

Overall survival (OS)

+2 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment ((vidutolimod, nivolumab)Experimental Treatment2 Interventions

Patients receive vidutolimod SC on days 1 and 7 of cycle 1, IT on day 14 of cycle 1 and days 1 and 14 of cycle 2, and then SC on day 1 of subsequent cycles. Patients also receive nivolumab IV over 30 minutes on days 1 and 14 of cycle 2 and on day 1 of subsequent cycles. Cycles of nivolumab repeat every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Cycles of vidutolimod repeat every 4 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

FDA approved

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for prostate cancer, such as Nivolumab and Vidutolimod, work by harnessing the body's immune system to target and destroy cancer cells. Nivolumab is a PD-1 inhibitor that prevents the immune system from being shut down by cancer cells, allowing immune cells to attack the tumor. Vidutolimod, a TLR9 agonist, stimulates the immune system to produce tumor-targeted T cells, enhancing the immune response. These treatments are significant for prostate cancer patients as they offer new avenues for combating cancer, particularly in cases where the disease has become resistant to conventional therapies.

Immunotherapy for Urothelial Carcinoma: Focus on Clinical Utility of Nivolumab.