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Phase Ib/II study of momelotinib with nivolumab or pembrolizumab in unresectable stage III/IV cutaneous melanoma

Verified siteRegistered drugNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on patients with Cutaneous Melanoma that is unresectable, meaning the cancer cannot be removed by surgery, and has spread to stage III or IV. The treatment being tested combines an oral tablet called momelotinib with an intravenous infusion of an anti‑PD‑1 antibody, either pembrolizumab or nivolumab. Anti‑PD‑1 antibodies are a type of immunotherapy that help the body’s immune system recognize and attack cancer cells.

The purpose of the trial is to determine whether this drug combination is safe and shows early signs of shrinking tumors. Participants take the tablet each day and receive the infusion every few weeks for several months, with regular doctor visits, blood tests, and imaging scans to watch for side effects and changes in tumor size. In the first part of the study, doctors find the highest dose that most people can tolerate (maximum tolerated dose) and choose a dose for later testing (recommended Phase II dose). In the second part, they look at how many patients experience a complete response (tumor disappears), partial response (tumor shrinks), stable disease (tumor does not grow), or progressive disease (tumor grows) after about six months.

The research process

The trial runs in 10 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial registration and baseline assessments
After you join the study, you will complete a consent form and provide basic information about your health history.
The study team will perform a physical examination, collect blood samples, and obtain imaging studies to document the current status of your melanoma.
Step 2
First administration of study medications
On the first day of treatment you will receive two types of medication:
momelotinib (brand name omjjara) as an oral tablet that you will swallow with water, and
An anti‑pd‑1 antibody (nivolumab or pembrolizumab) given by intravenous infusion, which means the drug is delivered through a vein over a short period.
The exact dose and frequency of each medication are defined in the study protocol and will be explained by the study staff.
Step 3
Daily oral momelotinib
You will take the momelotinib tablet every day, at the same time each day, for the duration of the study.
The tablet is film‑coated and comes in strengths of 100 mg, 150 mg, or 200 mg; the specific strength and number of tablets per day are determined by the dose level assigned to you.
If you miss a dose, you should follow the instructions provided by the study team.
Step 4
Regular intravenous anti‑pd‑1 infusions
You will receive an infusion of either nivolumab or pembrolizumab according to the schedule used in the study, which is typically every 2 or 3 weeks.
Each infusion is administered in a clinic or hospital setting; the medication is mixed with a small amount of fluid and delivered through a needle placed in a vein.
The infusion takes about 30 to 60 minutes, during which you will be monitored for any immediate reactions.
Step 5
Safety monitoring and laboratory tests
During the first few treatment cycles you will have weekly visits for blood draws and other laboratory tests to check how your body is responding to the medications.
The study team will assess any side effects (also called adverse events) and record their severity using a standardized grading system.
Additional assessments, such as physical exams and vital‑sign checks, will be performed at each visit.
Step 6
Dose‑finding phase (phase ib)
In the early part of the trial (phase ib) the investigators will evaluate the safety of the combination and may adjust the momelotinib dose to find the maximum tolerated dose (mtd) and the recommended phase ii dose (rp2d).
If dose adjustments are needed because of side effects, you will be instructed on how to modify the oral tablet dose while continuing the infusion schedule.
Step 7
Continued treatment and efficacy evaluation (phase ii)
Once the recommended dose is established, you will continue taking momelotinib daily and receiving anti‑pd‑1 infusions for up to 6 months.
This period corresponds to approximately 4, 6, 8, or 12 infusion cycles, depending on the interval used for the anti‑pd‑1 antibody.
The primary goal during this phase is to observe the anti‑tumor activity of the combination.
Step 8
Radiological response assessments
You will undergo imaging scans (such as ct or mri) at month 3 and month 6 after the first dose to evaluate the tumor response.
The scans will be reviewed using standard criteria (recist v1.1) to classify the outcome as complete response, partial response, stable disease, or progressive disease.
Step 9
Treatment completion or discontinuation
Treatment will end when you have completed the planned 6‑month period, or earlier if the disease progresses, side effects become unacceptable, or you choose to withdraw consent.
The study team will discuss the reason for stopping treatment and will provide guidance on the next steps.
Step 10
Long‑term follow‑up
After treatment stops, you will have follow‑up visits once a year for several years.
These visits will include safety assessments, quality‑of‑life questionnaires (qlq‑c30), and any additional tests the investigators deem necessary.
The follow‑up period continues until the last patient enrolled reaches the study end date.

Who can join the trial?

13 criteria

You must be at least 18 years old.
If you are a female who could become pregnant, you need a negative urine or blood (serum) pregnancy test done within the three days before the first treatment; a blood test will be required if the urine test is positive or unclear.
Female participants who could become pregnant must agree to use a highly effective birth control method during the study and for about five months after the last dose. This can include a partner who has had a vasectomy (surgical sterilization), hormonal pills or devices, an intra‑uterine system that releases hormones (IUS), or an intra‑uterine device (IUD) that fails less than 1% of the time. Choosing not to have sex (abstinence) is allowed if that is your usual practice.
Male participants who could father a child must also use an adequate birth control method from the first dose until about five months after the last dose. Abstinence is allowed if it is your normal lifestyle. Your female partner must be post‑menopausal, have had a permanent sterilization procedure (such as hysterectomy or tubal ligation), or use a highly effective birth control method.
You must be able to sign a written informed consent form, agreeing to follow all study rules and requirements.
You need to have shown a stable disease (SD) status according to the RECIST v1.1 criteria after six months of first‑line immune checkpoint inhibitor (ICI) therapy.
Your overall health must be rated as ECOG Performance Status 0, 1, or 2 (meaning you are fully active, restricted in physically strenuous activity but able to do light work, or capable of self‑care but unable to work).
You must have a diagnosis confirmed by tissue testing (either under a microscope – histology – or by cell analysis – cytology) of either:
- unresectable stage III melanoma (tumor that cannot be removed by surgery), or
- metastatic stage IV melanoma (cancer that has spread to other parts of the body).
- You must not be resistant or insensitive to the study drugs (immune checkpoint inhibitors or momelotinib).
- Your tumor’s BRAF mutation status (a specific genetic change) must be known.
- A tissue sample must be available (either an existing sample or a new biopsy) so researchers can test for the SAMHD1 status before the study ends.
- You should have a life expectancy of more than three months (the doctors expect you to live longer than three months).

Who cannot join the trial?

18 criteria

Unable to understand the information given or follow the study procedures.
Abnormal safety lab results at screening or baseline (using the CTCAE grading system, which rates how severe lab abnormalities are).
Active HIV infection or AIDS.
Active Hepatitis B or Hepatitis C infection that has not been controlled by treatment.
Significant ongoing or chronic bleeding that is graded Grade 2 or higher (meaning the bleeding is moderate to severe) within 4 weeks before randomization.
Unstable angina (chest pain caused by reduced blood flow to the heart) within 6 months before randomization.
Symptomatic congestive heart failure (the heart cannot pump blood well) and/or uncontrolled heart rhythm problems (arrhythmia) within 6 months before randomization.
A heart electrical measurement called the QT interval longer than 500 milliseconds, unless this is due to a bundle block (a type of heart conduction problem).
Ongoing worsening blood clot formation (thrombosis) despite treatment.
Any reason you cannot continue immune checkpoint inhibitor (ICI) therapy, including immune‑related side effects that have not returned to normal or become stable.
Active cancer spread to the brain (brain metastases) or to the membranes covering the brain and spinal cord (leptomeningeal metastases).
Eye melanoma (ocular melanoma), including the uveal and conjunctival types.
Any serious, uncontrolled medical condition (including infections) that the doctor believes could raise your risk, make it hard to receive the study treatment, or affect the study results.
Other cancers, unless they were treated with the goal of cure and you have been cancer‑free for more than 5 years.
Needing systemic steroids stronger than 10 mg daily prednisone equivalent or other immune‑suppressing medicines within 14 days of receiving the study drug (inhaled, topical steroids or low‑dose adrenal replacement are allowed if you do not have active autoimmune disease).
Women who are pregnant or breastfeeding.
Any condition that might make it difficult to follow the study schedule or take the medication as required.
Previous systemic cancer treatment for unresectable stage III or metastatic stage IV melanoma; prior adjuvant or neoadjuvant therapy is allowed if related side effects have returned to normal or are stable.

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Karolinska University Hospital
Verified
Solna, Sweden
Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
Verified
Gothenburg, Sweden
Region Skane Skanes Universitetssjukhus
Verified
Lund, Sweden

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Investigated drugs

momelotinib
is an oral medication taken as a tablet. In this study it is being tested as a new type of drug that may help the body’s immune system fight melanoma more effectively when used together with other cancer‑fighting medicines. Researchers are looking at how safe it is and what dose works best.
pembrolizumab
is given by an IV infusion at a clinic. It belongs to a class of drugs called checkpoint inhibitors that block a protein called PD‑1, which can stop immune cells from attacking cancer. In this trial it is used together with momelotinib to see if the combination improves treatment results for patients with advanced skin melanoma.
nivolumab
is also administered through an IV infusion. Like pembrolizumab, it blocks the PD‑1 protein, helping the immune system recognize and destroy cancer cells. The study is testing whether adding momelotinib to nivolumab can provide better control of melanoma compared with each drug alone.

What is already known about the treatment

Momelotinib
Momelotinib is taken as an oral film‑coated tablet. It is an approved orphan drug for myelofibrosis and is currently being studied in melanoma patients. The drug works by blocking JAK1, JAK2 and TBK1 enzymes, which slows down signals that help cancer cells grow. It belongs to the class of Janus kinase (JAK) inhibitors used as targeted anti‑cancer therapy.
Pembrolizumab
Pembrolizumab is given by intravenous infusion of a sterile solution. It is an approved medication for many cancers, including advanced melanoma, and is widely used in clinical practice. The drug is a monoclonal antibody that binds to the PD‑1 protein on immune cells, preventing the tumor from turning off the immune response. It is classified as an immune checkpoint inhibitor.
Nivolumab
Nivolumab is administered as an intravenous infusion of a concentrated solution. It is an approved treatment for several cancers, such as unresectable melanoma, and is routinely used in oncology. Nivolumab blocks the PD‑1 receptor on T‑cells, allowing the body’s immune system to recognize and attack cancer cells. It is also classified as an immune checkpoint inhibitor.

Investigated diseases

Unresectable Stage III or Stage IV Cutaneous Melanoma - Cutaneous melanoma is a cancer that begins in the pigment‑producing cells of the skin. When it reaches stage III, cancer cells have spread to nearby lymph nodes, and in stage IV they have spread to distant organs such as the lungs, liver, brain or distant skin sites. In the unresectable form the tumors cannot be removed safely with surgery because of their size, location or extent of spread. The disease typically grows outward from the skin and can infiltrate deeper layers, eventually entering the bloodstream or lymphatic system. As it advances, new tumor nodules may appear in other parts of the body, indicating progressive spread. This pattern of spread characterizes the progression of unresectable stage III or IV cutaneous melanoma.