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
- Conditions
- 10040900Merkel Cell Carcinoma (MCC)
- Registration Number
- NL-OMON51269
- Lead Sponsor
- 4SC AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 2
1. Signed written informed consent.
2. Age > 18 years at signature of Informed Consent Form (ICF).
3. 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; M1 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.
[Note: Not applicable for patients entering re-treatment (Section 4.4.1.1); in
case the patient is eligible for re-treatment as defined in this protocol, the
most recent treatment before re-treatment must be MERKLIN 1 study drug and no
other anti-tumor treatment is allowed since end of previous MERKLIN 1 treatment]
4. Fresh biopsy or archival tumor tissue (not older than 6 months) from an
unirradiated lesion.
[Note: No systemic anti-cancer treatment should have been given since archival
tumor tissue has been collected]
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at
study entry.
6. Estimated life expectancy of more than 12 weeks.
7. Disease must be measurable with at least one unidimensional measurable
lesion by RECIST v1.1 (including skin lesions).
[Baseline imaging will be performed within 18 days prior to planned start of
the study treatment, if no RECIST v1.1 evaluable imaging was done within 4
weeks prior to the planned start of the study treatment.]
8. Adequate hematological and organ function defined by the following
parameters:
Adequate hematological function defined by
• White blood cell count (WBC) > 3000/µl
• Absolute Neutrophil Count (ANC) > 1500/µl
• Lymphocyte count > 500/µl
• Hemoglobin (Hb) > 9 g/dl (or > 5.6 mmol/L), may have been transfused
• Platelet count > 100.000/µl
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)
9. 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.
1. Participation in another interventional clinical study within the past 30
days (participation in observational studies is permitted)
[Note: A patient in the survival follow-up phase will be eligible.]
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 (PD-1), anti-programmed death-ligand 1 (PD-L1) or
anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody.
[Note: Not applicable for patients entering re-treatment (Section 4.4.1.1); in
case the patient is eligible for re-treatment as defined in this protocol, the
most recent treatment before re-treatment must be MERKLIN 1 study drug and no
other anti-tumor treatment is allowed since end of previous MERKLIN 1 treatment]
4. Concurrent anti-cancer treatment (for example, cytoreductive therapy,
radiotherapy [except for palliative bone directed radiotherapy, or radiotherapy
administered on non-target superficial lesions], 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 biopsy, within 4 weeks
and/or if the subject has not fully recovered from surgery.
6. 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.
[Note: Patients receiving bisphosphonate or denosumab are eligible.]
7. 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.
8. 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.
9. 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
10. Prior organ transplantation (including allogeneic 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 o
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>Confirmed Objective Response (OR) according to RECIST v1.1, determined by<br /><br>independent review. Both CR and PR must be confirmed by a second tumor<br /><br>assessment preferably at the regularly scheduled 6-weeks assessment interval,<br /><br>but no sooner than 4 weeks after the initial diagnosis of CR or PR.</p><br>
- Secondary Outcome Measures
Name Time Method