Entinostat + Pembrolizumab for Myelodysplastic Syndrome

No longer recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: DNMTi

Must not be taking: Anti-PD-1, HDACi

Disqualifiers: Active cancers, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: entinostat, a drug that may stop cancer cell growth, and pembrolizumab, an immunotherapy drug that might boost the immune system to attack cancer. The goal is to find the best dose and check for side effects in patients with myelodysplastic syndrome, a type of blood cancer. The trial targets individuals whose previous treatment with DNA methyltransferase inhibitors was ineffective. Suitable candidates are those diagnosed with myelodysplastic syndrome who have not benefited from certain other therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have used any experimental drugs or therapies within 21 days before the trial or if you have had chemotherapy or radiotherapy within 4 weeks before entering the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining entinostat with pembrolizumab has been studied before. In patients with certain types of lung cancer, this combination was tested and provided valuable insights into its safety. The combination was generally well-tolerated, with some patients experiencing manageable side effects. Common side effects included tiredness and nausea, which many found to be mild.

Entinostat affects cell growth, while pembrolizumab helps the immune system fight cancer. Pembrolizumab is already approved for other uses, so its safety is well-known.

This trial is in an early stage, with a major focus on safety. While more information is needed, existing research offers some reassurance about its tolerability. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for myelodysplastic syndrome?

Researchers are excited about entinostat and pembrolizumab for treating myelodysplastic syndrome because they bring a fresh approach compared to traditional treatments like hypomethylating agents and supportive care. Entinostat is a type of drug known as an HDAC inhibitor, which helps reactivate genes that can suppress tumor growth. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that boosts the body's immune response to fight cancer cells. This combination offers a promising new mechanism of action by both altering gene expression and enhancing the immune system, potentially leading to better outcomes for patients.

What evidence suggests that entinostat and pembrolizumab might be an effective treatment for myelodysplastic syndrome?

Research has shown that using entinostat with pembrolizumab may help treat myelodysplastic syndrome. In this trial, participants will receive a combination of these two drugs. Entinostat inhibits certain enzymes that cancer cells require for growth. A study found that this combination helped some patients with non-small cell lung cancer who did not respond to other treatments. Pembrolizumab, a type of immunotherapy, aids the body's immune system in fighting cancer cells. These early results suggest that this combination might benefit patients who have not improved with other myelodysplastic syndrome treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Amer M. Zeidan

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with Myelodysplastic Syndrome or Preleukemia who haven't improved after treatment with hypomethylating agents. They should have proper kidney and liver function, no severe illnesses, and not be pregnant or breastfeeding. HIV-positive patients can join if they meet certain health criteria.

Inclusion Criteria

I am HIV positive, on effective treatment, with an undetectable viral load and a CD4 count over 250.

My MDS or AML treatment with DNMTi didn't work or my cancer progressed after it.

My kidney function, measured by creatinine clearance, is normal or above.

Exclusion Criteria

I have hepatitis B or C, but my viral load is undetectable, with or without treatment.

I have an autoimmune disease but my thyroid condition is stable with treatment.

I am allergic to pembrolizumab or similar medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive entinostat orally and pembrolizumab intravenously in a dose-escalation study. Treatment repeats every 21 days for up to 4 cycles.

12 weeks

4 visits (in-person)

Extended Treatment

Participants who achieve an objective response or maintain stable disease may continue treatment for up to 1 year.

1 year

Follow-up

Participants are monitored monthly for safety and effectiveness after treatment completion.

6 months

6 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Entinostat
• Pembrolizumab

Trial Overview The trial tests the combination of Pembrolizumab (an immune system booster) and Entinostat (a growth blocker for cancer cells) in patients whose previous DNA methyltransferase inhibitor therapy didn't work. It aims to find the safest dose and see how well these drugs work together.

How Is the Trial Designed?

Group I: Treatment (entinostat, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year.

Entinostat is already approved in China, European Union for the following indications:

Approved in China as Entinostat for:

• Cancer

Approved in European Union as Entinostat for:

• Orphan Drug designation for cancer treatment

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Entinostat

Entinostat | C21H20N4O3 | CID 4261 - PubChem Entinostat is a member of the class of benzamides resulting from the formal condensation of the carboxy group of the pyridin-3-ylmethyl carbamate derivative ...

2. synapse.patsnap.com synapse.patsnap.com/drug/73864b8d082e4ee6a8e7f0560a2fa204

Entinostat - Drug Targets, Indications, Patents Entinostat: a HDAC inhibitors, Epigenetic drug Drug, Initially developed by Bayer AG, Now, its global highest R&D status is Approved, Mechanism: HDAC ...

3. go.drugbank.com go.drugbank.com/unearth/q?button=&c=_score&d=down&page=210&query=enterocin+non+5+36&searcher=drugs

Advanced Filter Entinostat has been investigated for the treatment of Non-Small Lung Cancer, Epigenetic Therapy. Investigational. Matched Synonyms: … N-(2-aminophenyl)-4-(N-( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7887114/

Entinostat plus pembrolizumab in patients with metastatic ... We report outcomes in patients with anti-PD-(L)1– resistant/refractory NSCLC treated with pembrolizumab plus entinostat in ENCORE 601.

5. go.drugbank.com go.drugbank.com/unearth/q?approved=1&c=_score&d=down&illicit=1&investigational=1&nutraceutical=1&page=55&query=2-MAPB&searcher=drugs&vet_approved=1&withdrawn=1

Advanced Filter Entinostat has been investigated for the treatment of Non-Small Lung Cancer, Epigenetic Therapy. Investigational. Matched Synonyms: … N-(2-aminophenyl)-4-(N-( ...

6. go.drugbank.com go.drugbank.com/unearth/q?c=_score&d=down&page=422&query=ns+nasen+heratburn&search_type=drugs&searcher=drugs

422 Matched Description: … Entinostat is under investigation for the treatment and other of Volunteers, Breast Cancer, Human Volunteers … Matched Synonyms: … N-(2- ...