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Merkel Cell CarcinomaPhase 2NCT04874831

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

A Phase 2 study testing domatinostat in combination with avelumab in people with Merkel Cell Carcinoma, run by 4SC AG.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Merkel Cell Carcinoma
What is being tested?
domatinostat in combination with avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 Nov 2021to Sep 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent.
  • Age 18 years at signature of Informed Consent Form (ICF).
  • Histologically 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 metastatic 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 adjuvant 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.
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  • Fresh biopsy or archival tumor tissue (not older than 3 months) from an unirradiated lesion.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry.
  • Estimated life expectancy of more than 12 weeks.
  • Disease must be measurable with at least one unidimensional measurable lesion by RECIST vl.l (including skin lesions).
  • Adequate hematological and organ function defined by the following parameters:
  • Adequate hematological function defined by
  • White blood cell count (WBC) > 3000/pl
  • Absolute Neutrophil Count (ANC) > 1500/pl
  • Lymphocyte count > 500/pl
  • Hemoglobin (Hb) > 9 g/dl (or > 5.6 mmol/L), may have been transfused
  • Platelet count > 100.000/pl
  • Adequate hepatic function defined by
  • Serum total bilirubin < 1.5 x ULN
  • ALT and/or AST < 1.5 x ULN
  • Adequate renal function defined by
  • eGFR > 60 ml/ min (as per Cockcroft-Gault formula)
  • Highly effective contraception for both male and female subjects if the risk of conception exists. Female patients of childbearing potential 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.

Who cannot join

  • Participation in another interventional clinical study within the past 30 days (participation in observational studies is permitted)
  • Concurrent treatment with a non-permitted drug.
  • Prior therapy with any histone deacetylase (HDAC) inhibitor or antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as anti-programmed death 1 (PD-1), antiprogrammed death-ligand 1 (PD-L1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody.
  • 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.
  • Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the subject has not fully recovered from surgery.
  • Concurrent systemic therapy with steroids or other immunosuppressive agents (e.g. methotrexate, azathioprine, interferons, mycophenolate, anti-TNF agents and other), or the use of any investigational 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.
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  • Conditions requiring systemic anti-arrhythmic therapy known to prolong QT/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.
  • Patients with active central nervous system (CNS) metastases 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 CNS metastases (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.
  • History of or concurrent malignancies, 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
  • Prior organ transplantation (including allogeneic stem-cell transplantation).
  • 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.
  • Positive testing for HIV or known AIDS or HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening is positive).
  • Active or history of any autoimmune disease (except for patients with vitiligo) or immune-diseases that required treatment with systemic immune modulating drugs.
  • History or current evidence of clinically relevant allergies or hypersensitivity, 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.
  • Persisting toxicity related to prior therapy Grade > 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0; however, sensory neuropathy Grade < 2 will be acceptable.
  • Pregnancy or lactation period.
  • Known or suspected alcohol or drug abuse.
  • 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 (New York Heart Association (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
  • 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.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Legal incapacity or limited legal capacity.
  • Administration of a live vaccine within 28 days prior to study drug administration. Live vaccines are also prohibited during study treatment.

About this study

Official title: A Phase II, Open Label, Multicenter Study to Investigate the Efficacy and Safety of Domatinostat in Combination With Avelumab in Patients With Treatment-naïve Metastatic Merkel Cell Carcinoma - the MERKLIN 1 Study

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

Being tested
domatinostat in combination with avelumab
Medical subject headings
Carcinoma, Merkel Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • domatinostat in combination with avelumabDrug

    domatinostat tablets and avelumab infusion

Study groups in NCT04874831
Study groupRoleWhat they receive
domatinostat and avelumabExperimentalSingle arm study of Domatinostat tablets in combination with avelumab infusion
Receives: Drug: domatinostat in combination with avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 1 year

Secondary outcomes (12)

  1. Duration of Response (DOR)

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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: up to 1 year

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

    number, frequency, duration and severity of AEs

    Measured: approx. 3 years

  8. Correlation of biomarker expression to efficacy

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

    Measured: up to 1 year

  9. Anti-drug-antibodies (ADAs)

    Anti-drug-antibodies (ADAs) treatments.

    Measured: 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)

    Measured: up to 1 year

  11. Plasma concentration of domatinostat and avelumab

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

    Measured: 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)

    Measured: up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2021
  2. Study start1 Nov 2021 (estimated)
  3. Primary completionSep 2025 (estimated)
  4. Study completionSep 2025 (estimated)

Why it stopped: 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.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04874831
Sponsor's protocol ID
4SC-202-4-2019
Other IDs
2019-003575-19, 2019
Status last verified
Nov 2021
First submitted
15 Apr 2021
Last updated
18 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing domatinostat in combination with avelumab in people with Merkel Cell Carcinoma, run by 4SC AG.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Objective Response (OR) (time frame: up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04874831.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2021.

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