Ensartinib for Melanoma

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Prior ALK inhibition, Cardiovascular disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ensartinib, a targeted therapy, for people with melanoma, a type of skin cancer with a specific genetic abnormality known as ALK. The goal is to observe the drug's effects on both the cancer and the patient. Candidates may qualify if they have advanced melanoma that worsened after other treatments and their tumors exhibit the ALK alteration. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that you cannot have received certain cancer therapies or strong CYP3A inhibitors or inducers recently. It's best to discuss your current medications with the trial team.

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

Research has shown that the FDA has approved ensartinib to treat ALK-positive non-small cell lung cancer. In earlier studies for this condition, patients taking ensartinib experienced some known side effects. Specifically, about 44% of patients had higher blood sugar levels. Other common side effects included skin rash and nausea. These results provide insight into the drug's safety. While ensartinib is now being tested for melanoma, its use in lung cancer suggests it is generally well-tolerated. However, patients should be aware of these possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Ensartinib is unique because it targets a specific genetic alteration known as ALKATI in melanoma, setting it apart from standard treatments like immunotherapies and BRAF/MEK inhibitors. While traditional therapies focus on broader mechanisms, ensartinib homes in on this particular genetic change, potentially offering a more precise treatment for patients with this alteration. Researchers are excited about ensartinib because its oral administration and targeted approach may lead to better outcomes and fewer side effects for patients with ALKATI-positive tumors.

What evidence suggests that ensartinib might be an effective treatment for melanoma?

Research has shown that ensartinib yields promising results for treating certain types of cancer. In studies involving patients with ALK-positive non-small cell lung cancer (a specific genetic change), ensartinib significantly improved outcomes. Patients lived longer without disease progression compared to those taking another drug, crizotinib. Approximately 60% of patients responded to ensartinib, living an average of 9.2 months without cancer progression. Although these studies focused on lung cancer, this trial will investigate whether ensartinib might also be effective for melanoma with similar genetic changes. ^{2 6 7 8 9}

Who Is on the Research Team?

Alexander Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced malignant melanoma that has a specific ALK alteration. Participants must have tried PD-1 based therapy (and BRAF inhibitors if applicable) without success, and should not be pregnant or breastfeeding. They need to have good liver, kidney, and blood function and can't have used certain other cancer treatments or strong CYP3A affecting drugs recently.

Inclusion Criteria

My cancer progressed after PD-1 therapy, and if it's BRAF V600 positive, I've had BRAF inhibitors.

My liver, kidney, and blood tests are within the required ranges.

My cancer can be measured by scans and has not been treated locally in the last 30 days or has grown despite treatment.

Exclusion Criteria

I have previously received ALK inhibitors for treatment.

I had lung inflammation before, but it's resolved now.

I haven't had any cancer treatments in the last 3 weeks or within the last treatment cycle, whichever is shorter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ensartinib orally at a dose of 225mg daily

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ensartinib

Trial Overview The trial is testing ensartinib's effectiveness on melanoma with ALK alterations. Ensartinib is an investigational drug targeting this abnormality in the hope of treating the cancer more effectively.

How Is the Trial Designed?

Group I: ensartinib Experimental Treatment 2 Interventions

The screening portion of the trial will test archival tumor material for the presence of ALKATI using a Nanostring-based RNA assay for any patients deemed to be current or future candidates for this trial. This will require approximately 5 formalin-fixed paraffin- embedded (FFPE) slides of 5-8 micron thickness. For the treatment portion of the study, all patients will receive ensartinib orally at a dose of 225mg daily.

Ensartinib is already approved in United States for the following indications:

Approved in United States as Ensacove for:

• ALK-positive non-small cell lung cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Xcovery Holdings, Inc.

Industry Sponsor

Trials

10

Recruited

620+

Xcovery Holding Company, LLC

Industry Sponsor

Trials

9

Recruited

530+

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-ensartinib-alk-positive-locally-advanced-or-metastatic-non-small-cell-lung-cancer

FDA approves ensartinib for ALK-positive locally advanced ... Ensartinib demonstrated a statistically significant PFS improvement compared to crizotinib with a hazard ratio (HR) of 0.56 (95% CI: 0.40, 0.79; ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11883823/

Ensartinib for EML4-ALK-positive lung adenocarcinoma with ... After 3 months of ensartinib treatment, the patient achieved a partial response and reached stable disease at six months, which sustained for 30 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41148187/

Efficacy and safety of ensartinib in the treatment of non- ... Ensartinib demonstrated favourable efficacy across dose-escalation, phase II and phase III trials. In treating naïve patients, ORRs ranged from ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/218171Orig1s000IntegratedR.pdf

218171Orig1s000 - accessdata.fda.gov Effectiveness. The nonclinical data support the potential effectiveness of ensartinib based on the following findings (see Section 13 for detailed reviews of ...

5. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/ensartinib

Ensartinib - an overview | ScienceDirect Topics Among the ALK-positive efficacy evaluable patients treated at ≥ 200 mg, the RR was 60% and median PFS was 9.2 months. Of note, in ALK TKI-naïve patients the RR ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/218171s000lbl.pdf

ENSACOVETM (ensartinib) capsules, for oral use In the pooled safety population [see Adverse Reactions (6.1)], based on laboratory data, 44% of patients receiving ENSACOVE experienced increased blood glucose, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03420508

Treating Patients With Melanoma and ALK Alterations ... The purpose of this study is to test the effects of the study drug, ensartinib, on the patient and the cancer. Ensartinib is a new, investigational type of ...

8. go.drugbank.com go.drugbank.com/drugs/DB14860

Ensartinib: Uses, Interactions, Mechanism of Action The drug is 10-fold more potent in the inhibition of the growth of ALK-positive lung cancer cell lines when compared to crizotinib. Ensartinib ...

9. cancer.gov cancer.gov/about-cancer/treatment/drugs/ensartinib-hydrochloride

Ensartinib Hydrochloride - NCI This page contains brief information about ensartinib hydrochloride and a collection of links to more information about the use of this drug.