What side effects are associated with this type of intervention?

Treatments for prostate cancer that involve enzyme inhibition, such as DS3201, commonly cause side effects like fatigue, nausea, and liver toxicity. Immune system activators like ipilimumab can lead to immune-related adverse events, including colitis, dermatitis, hepatitis, and endocrinopathies, due to the immune system attacking normal tissues as well as cancer cells.

What prior FDA approvals exist?

For the treatment of prostate cancer, the FDA has approved several drugs that either inhibit enzymes or activate the immune system. Enzalutamide and abiraterone are examples of enzyme inhibitors that target androgen receptor signaling pathways, crucial for prostate cancer cell growth. On the immune system activation front, Sipuleucel-T is an FDA-approved immunotherapy that stimulates the patient's immune system to attack prostate cancer cells. While Ipilimumab, an immune checkpoint inhibitor, is approved for other cancers, its use in prostate cancer is still under investigation.

What other types of research exist?

Promising novel alternatives for prostate cancer treatment in 2024 include targeting prostate-specific membrane antigen (PSMA) with agents like Lutetium-177-PSMA-617, which has shown efficacy in metastatic castration-resistant prostate cancer (CRPC). Additionally, combining immune checkpoint inhibitors with androgen receptor targeting agents, such as pembrolizumab with enzalutamide, is being explored. CDK12-altered prostate cancers may respond well to PD-1 targeted therapies and PARP inhibitors. These approaches are under investigation and may offer new avenues for treatment.

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Enzyme Inhibitor

Valemetostat + Ipilimumab for Metastatic Prostate, Urothelial, and Renal Cell Cancers

Phase 1

Recruiting

Led By Ana Aparicio

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Patients with prostate carcinomas must also display the AVPC molecular signature (i.e. known loss or mutation [by Clinical Laboratory Improvement Act (CLIA) certified molecular testing by immunohistochemistry (IHC) and/or deoxyribonucleic acid (DNA) sequencing in solid tumor samples, and/or in circulating tumor DNA]) in at least 2 of the following: Tp53, RB1 and PTEN

Ability to swallow and retain oral medications

Must not have

Myocardial infarction (MI)/stroke within 6 months prior to day 1 of study treatment

Clinically significant cardiovascular disease including:

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests DS3201 and ipilimumab together for patients with advanced prostate, urothelial, or renal cell cancer. DS3201 blocks enzymes to stop cancer growth, while ipilimumab boosts the immune system to fight cancer. The goal is to find the best dose and check for side effects.

Who is the study for?

This trial is for adults with metastatic prostate, urothelial, or renal cell cancers who have an ECOG performance status of 0-1. They must have confirmed cancer spread and be recovered from previous treatments. Eligible participants need proper organ function and no active infections like hepatitis or HIV. Pregnant women, those with certain heart conditions or autoimmune diseases, and individuals on recent cancer therapies are excluded.

What is being tested?

The trial tests the combination of DS3201 (Valemetostat) and Ipilimumab to determine safe dosages and side effects in treating advanced cancers. Valemetostat targets enzymes for tumor growth while Ipilimumab boosts the immune system's ability to fight cancer cells.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs, skin issues, hormonal imbalances, digestive disturbances, fatigue, infusion-related reactions and increased susceptibility to infections.

Eligibility Criteria

Inclusion Criteria

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

Select...

My prostate cancer shows specific genetic changes in Tp53, RB1, or PTEN.

Select...

I can swallow and keep down pills.

Select...

My kidney cancer worsened despite treatment with specific cancer drugs.

Select...

My cancer is visible on scans and can be biopsied.

Select...

I am fully active or can carry out light work.

Select...

My kidney function, measured by creatinine levels or clearance, is within the required range.

Select...

My cancer has grown or spread according to recent scans.

Select...

My brain metastases are stable, and I've been off steroids or on a low dose for 4 weeks without neurological issues.

Exclusion Criteria

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

Select...

I have not had a heart attack or stroke in the last 6 months.

Select...

I have a serious heart condition.

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I have a history of lung scarring or inflammation.

Select...

I do not have an active hepatitis B or C infection.

Select...

My cancer has spread to the lining of my brain and spinal cord.

Select...

I have untreated spinal cord or brain issues due to cancer.

Select...

My heart test (ECG) does not show major issues that could affect my safety in the study.

Select...

I have a history of serious irregular heartbeats.

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I have been treated with an EZH2 inhibitor before.

Select...

I have a GI condition that affects how my body absorbs nutrients.

Select...

I stopped my immunotherapy permanently due to a severe side effect.

Select...

I have severe heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Secondary study objectives

Immunologic and molecular effects

Overall response rate (ORR)

Time to treatment failure (TTF)

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

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 (valemetostat, ipilimumab)Experimental Treatment2 Interventions

Patients receive valemetostat PO QD on days 1-21 and ipilimumab IV over 90 minutes on day 1 of cycles 1 and 3. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3420

0 / 20Eligibility 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 include enzyme inhibition and immune system activation. Enzyme inhibitors, like DS3201, block specific enzymes needed for tumor cell growth, preventing cancer proliferation. Immune system activators, such as ipilimumab, use monoclonal antibodies to enhance the body's immune response by blocking checkpoints like CTLA-4, allowing T-cells to attack cancer cells more effectively. These targeted approaches are vital for prostate cancer patients as they help control disease progression and improve outcomes.