ClinicalTrials.gg
WithdrawnNCT04874831Updated Nov 18, 2021

Domatinostat in Combination With Avelumab in Patients With Treatment-naïve Metastatic Merkel Cell Carcinoma (MERKLIN 1)

A Phase 2 interventional study of domatinostat in combination with avelumab in Merkel Cell Carcinoma, sponsored by 4SC AG. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-18.

Sponsored by 4SC AG · Phase 2, Interventional, and Treatment

Why this study was withdrawn
Refocusing of sponsor's clinical development program. No safety concern or change of the risk-benefit assessment of the investigational medicinal product has led to this decision.

Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →

Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase II trial studies how well domatinostat (4SC-202) works in combination with avelumab in adult patients with treatment-naïve metastatic Merkel Cell Carcinoma

02

Conditions studied

  • Merkel Cell Carcinoma
03

In context

Carcinoma, Merkel Cell

150 studies on the registry are indexed under Carcinoma, Merkel Cell; 40 are open to participants now.

Browse Carcinoma, Merkel Cell studies →

Lead sponsor

4SC AG is the lead sponsor of 13 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Signed written .
  2. Age 18 years at signature of Informed Consent Form (ICF).
  3. proven MCC.

    • Confirmation of the diagnosis by immune-histochemistry as per standard at the institution, including (but not limited to) CK20 and TTF-1.
    • Patients must have or distally recurrent disease; Ml status must be confirmed at entry.
    • Patients must not have received any prior systemic treatment for metastatic MCC. Prior treatment in the setting (no clinically detectable disease; no metastatic disease) will be allowed, if the end of the treatment occurred at least 6 months prior to study entry, i.e. signing ICF.
  4. Fresh or archival tumor tissue (not older than 3 months) from an unirradiated lesion.
  5. Performance Status (ECOG PS) of 0 to 1 at study entry.
  6. Estimated of more than 12 weeks.
  7. Disease must be measurable with at least one unidimensional by vl.l (including skin lesions).
  8. Adequate hematological and organ function defined by the following parameters:

    Adequate hematological function defined by

    • White blood cell count (WBC) > 3000/pl
    • (ANC) > 1500/pl
    • Lymphocyte count > 500/pl
    • (Hb) > 9 g/dl (or > 5.6 mmol/L), may have been transfused
    • count > 100.000/pl

    Adequate hepatic function defined by

    • Serum total \< 1.5 x
    • and/or AST \< 1.5 x ULN

    Adequate renal function defined by

    • > 60 ml/ min (as per formula)
  9. Highly effective for both male and female subjects if the risk of conception exists. Female patients of must have a negative urine or serum pregnancy test before receiving the first dose of study medication and must comply with contraception methods as requested by the study protocol.

Exclusion criteria

Exclusion Criteria:

  1. Participation in another interventional clinical study within the past 30 days (participation in observational studies is permitted)
  2. Concurrent treatment with a non-permitted drug.
  3. Prior therapy with any histone deacetylase (HDAC) inhibitor or antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as anti-programmed death 1 (), antiprogrammed death-ligand 1 (PD-L1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody.
  4. Concurrent anti-cancer treatment (for example, cytoreductive therapy, radiotherapy, immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the study treatment.
  5. Major surgery for any reason, except diagnostic , within 4 weeks and/or if the subject has not fully recovered from surgery.
  6. Concurrent systemic therapy with or other agents (e.g. methotrexate, azathioprine, interferons, mycophenolate, anti-TNF agents and other), or the use of any drug within 28 days before the start of study treatment. Short-term administration of systemic steroids e.g. for allergic reactions or the management of immune-related adverse events [irAE] while on study is allowed. Also, patients requiring hormone replacement with corticosteroids for adrenal insufficiency are eligible if the steroids are administered only for purpose of hormonal replacement and at doses \< 10 mg or equivalent prednisone per day.
  7. Conditions requiring systemic anti-arrhythmic therapy known to prolong /QTc interval, patients with QTcF interval >480 msec on at least 2 separate and consecutive ECGs at screening or a medical history of long-QT-Syndrome.
  8. Patients with active central nervous system (CNS) are excluded and a brain CT/MRI will be required during screening if not performed within 6 weeks prior to the planned start of the study treatment. Subjects with a history of treated (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
  9. History of or concurrent , except the malignancy is clinically insignificant, no systemic treatment is or has been required for the last 6 months, and the patient is clinically stable
  10. Prior organ transplantation (including stem-cell transplantation).
  11. Any active gastrointestinal disorder that could interfere with the absorption of domatinostat characterized by malabsorption or inability to swallow tablets as per judgment of the Investigator.
  12. Positive testing for or known AIDS or or infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening is positive).
  13. Active or history of any disease (except for patients with vitiligo) or immune-diseases that required treatment with systemic immune modulating drugs.
  14. History or current evidence of allergies or , which includes known or suspected intolerabilities attributed to domatinostat or avelumab or to constituents of the domatinostat tablets or avelumab infusion and known severe hypersensitivity reactions (Grade 3) to monoclonal antibodies.
  15. Persisting toxicity related to prior therapy Grade > 1 National Cancer Institute (NCI-CTCAE) version 5.0; however, sensory neuropathy Grade \< 2 will be acceptable.
  16. Pregnancy or lactation period.
  17. Known or suspected alcohol or drug abuse.
  18. Clinically significant (i.e. active) cardiovascular and/or thromboembolic diseases:

    • Cerebral vascular accident or stroke \< 6 months prior to enrollment.
    • Uncontrolled hypertension
    • Congestive heart failure ( (NYHA) ClassIII or IV)
    • Serious cardiac arrhythmia requiring medication (patients with status post pacemaker and/or defibrillator implantation can be included)
    • Symptomatic ischemic or severe valvular heart disease
    • Unstable angina pectoris or a myocardial infarction within 6 months prior to screening, i.e. signing ICF
  19. All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient s tolerance to the study treatment.
  20. Any psychiatric condition that would prohibit the understanding or rendering of .
  21. Legal incapacity or limited legal capacity.
  22. Administration of a within 28 days prior to study drug administration. Live vaccines are also prohibited during study treatment.
Terms in these criteria, in plain language(36)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Adjuvant and neoadjuvant

Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    domatinostat and avelumab

    Single arm study of Domatinostat tablets in combination with avelumab infusion

    Drug: domatinostat in combination with avelumab

Interventions

  • Drugdomatinostat in combination with avelumab

    Drug pages: Domatinostat · Avelumab

    domatinostat tablets and avelumab infusion

06

What researchers measure

Primary outcomes

  1. Confirmed Objective Response (OR)

    Confirmed Objective Response (OR) according to RECIST vl.l, determined by independent review. Both Complete Response and Partial Response must be confirmed by a second tumor assessment preferably at the regularly scheduled 6-weeks assessment interval, but no sooner than 4 weeks after the initial diagnosis of CR or PR.

    Time frame: up to 1 year

Secondary outcomes

  1. Duration of Response (DOR)

    Duration of Response (DOR) according to RECIST vl.l as determined by independent review.

    Time frame: up to 1 year

  2. Durable Response (DR)

    Durable Response (DR) according to RECIST vl.l, defined as objective response (CR or PR) determined by independent review with duration of at least 6 months.

    Time frame: up to 1 year

  3. Overall Survival (OS)

    Overall Survival (OS) time, defined as the time from the first administration of study treatment until death due to any cause determined by the Investigator.

    Time frame: approx 3.5 years

  4. Progression Free Survival (PFS)

    Progression Free Survival (PFS) according to RECIST vl.l, defined as the time from first dosing (Day 1) to the date of PD or death from any cause (whichever comes first) as determined by independent review.

    Time frame: approx. 3 years

  5. Disease Control (DC)

    Disease Control (DC) according to RECIST vl.l, defined as the proportion of patients with either an objective response (CR, PR) or stable disease (SD), as determined by independent review.

    Time frame: up to 1 year

  6. RECIST vl.l response

    RECIST vl.l responses at 6 and 12 months after start of study treatment as determined by independent review.

    Time frame: up to 1 year

  7. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

    number, frequency, duration and severity of AEs

    Time frame: approx. 3 years

  8. Correlation of biomarker expression to efficacy

    Correlation of ORR, DOR, DR, DC and PFS to biomarker expression determined by immunohistochemistry.

    Time frame: up to 1 year

  9. Anti-drug-antibodies (ADAs)

    Anti-drug-antibodies (ADAs) treatments.

    Time frame: up to 1 year

  10. Health related Quality of Life determined by the questionnaire FACT-M

    The impact of treatment on the patient's QoLwill be assessed with the questionnaire "Functional Assessment of Cancer Therapy - Melanoma (FACT-M)" where QoL is assessed on a scale 0-240 (higher score means better status of health)

    Time frame: up to 1 year

  11. Plasma concentration of domatinostat and avelumab

    Single trough values of domatinostat and avelumab at pre-defined time points

    Time frame: up to 1 year

  12. Health related Quality of Life determined by the questionnaire EQ-5D-5L

    The impact of treatment on the patient's QoLwill be assessed with the questionnaire "EQ-5D-5L" which is a multi attribute utility instrument for measuring health-related QoL as EQ5D index with a score 0-1 (higher score means better status of health)

    Time frame: up to 1 year

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Start is estimated for Nov 2021; primary completion for Sep 2025, 46 months later.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 15, 2021
First posted
May 6, 2021
StartEst.
Nov 1, 2021
Primary completionEst.
Sep 2025
CompletionEst.
Sep 2025
Last update
Nov 18, 2021
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 18, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04874831
Lead sponsor
4SC AG
Responsible party
Sponsor
First posted
May 6, 2021
Start date
Nov 1, 2021 (estimated)
Primary completion
Sep 2025 (estimated)
Completion
Sep 2025 (estimated)
Last update
Nov 18, 2021

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Domatinostat · Avelumab

Start the discussion