NL-OMON49071已完成2 期
A phase II, open label study to investigate the efficacy and safety of domatinostat in combination with avelumab in patients with advanced unresectable/metastatic Merkel Cell Carcinoma progressing on anti-PD(L)1 antibody therapy - the MERKLIN 2 study - MERKLIN 2
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 4SC AG
- 入组人数
- 4
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •1. Age >= 18 years (at signature of ICF), mentally and physically able and
- •willing to provide informed consent for study participation.
- •2. Histologically confirmed Merkel Cell Carcinoma (MCC).
- •3. ECOG performance status <= 1.
- •4. MCC in an advanced, unresectable stage III or metastatic stage IV (includes
- •patients who refused surgical resection or are not eligible for such surgical
- •resection) [Note: patients with PD post-R0 surgical resection and adjuvant
- •anti-PD-(L)1 antibody monotherapy of at least 12 weeks will be eligible as long
- •as Inclusion Criterion #6 is fulfilled]
- •5. RECIST v1.1 evaluable disease.
- •6. Progressing on previous anti-PD-(L)1 antibody monotherapy within the last 12
- •weeks before planned first administration of study medication fulfilling at
- •least one of the following criteria:
- •Radiology Criteria: - Detection of new lesion(s) or - At least a 20%
- •increase in the sum of diameters; in addition, the sum must also demonstrate an
- •absolute increase of at least 5 mm.
- •In case of unresectable locoregional tumor not measurable by scan, assessment
- •with a caliper will be allowed: a single, unirradiated/ untreated lesion must
- •have a diameter of > 10 mm, at least a 20% increase in the diameter and an
- •absolute increase of at least 5 mm.
- •Biopsy of new lesion(s) and histological confirmation of PD in case of
- •progression during adjuvant anti-PD-(L)1 treatment.
- •7. Confirmation of PD not earlier than 4 weeks after initial assessment of PD
- •on previous anti-PD-(L)1 monotherapy. [Note: Confirmatory scan can be the
- •baseline scan for this study, if evaluable for RECIST v1.1 and can be performed
- •during screening phase]
- •8. Pretreatment with avelumab monotherapy (cohort 1) or any antiPD-1 antibody
- •monotherapy (cohort 2) fulfilling the following minimum exposure criteria:
- •Anti-PD-(L)1 antibody given every 2 weeks Q2W: at least 6 administrations
- •within the last 6 months, last dose within 3 months before planned first
- •administration of study medication.
- •Anti-PD-(L)1 antibody given every 3 weeks Q3W: at least 4 administrations
- •within the last 6 months, last dose within 3 months before planned first
- •administration of study medication. • Anti-PD-(L)1 antibody given every 4 weeks
- •Q4W: at least 3 administrations within the last 6 months, last dose within 3
- •months before planned first administration of study medication.
- •9. Patients must have been treated with anti-PD-(L)1 antibody therapy as the
- •most recent systemic anti-neoplastic therapy
- •10. Patients must have been treated with approved doses and schedules of
- •avelumab or anti-PD-1 antibodies. For investigational anti-PD-1 antibodies,
- •patients must have been treated with the recommended phase 2 dose and schedule.
- •11. Patients with brain or central nervous system metastases will be eligible,
- •if asymptomatic, treated with surgery, whole brain or stereotactic
- •radiotherapy, clinically stable (at least for a period of 2 months prior to
- •signing ICF) and do not require continued steroid therapy. [Note: patients
- •with known leptomeningeal carcinomatosis must be excluded]
- •12. Locally advanced/unresectable MCC must not be eligible for radiation
- •therapy due to prior cumulative radiation treatment, judgment of radiation
- •oncologist that the tumor is unlikely to respond to t
排除标准
- •1. History of serious anti-PD-(L)1 therapy-related adverse reactions
- •prohibiting further avelumab treatment:
- •- Pneumonitis: Grade 3 or 4 or recurrent Grade 2
- •- Hepatitis: AST or ALT more than 5 times the upper limit of normal or total
- •bilirubin more than 3 times the upper limit of normal
- •- Colitis/diarrhea: Grade 4 or recurrent Grade 3
- •- Nephritis and renal dysfunction: serum creatinine more than 6 times the upper
- •limit of normal
- •- Any other immune-mediated adverse reactions which resulted in a
- •life-threatening situation for the patient (excluding endocrinopathies) or
- •infusion-related reactions Grade 3 or 4.
- •2. More than one line of previous systemic anti-neoplastic therapy other than
- •anti-PD-(L)1 antibody monotherapy.
- •3. Palliative radiation therapy of single lesions within 2 weeks before planned
- •administration of study medication.
- •4. Patients currently participating or having participated in a clinical study
- •in which the last administration of the investigational medicinal product was
- •within 2 weeks before consenting to study participation (i.e. signing ICF).
- •5. Not recovered adequately (<= Grade 1) from toxicities and/or complications
- •from surgical intervention or from previous anticancer therapies (excluding
- •alopecia, fatigue or endocrine dysfunction on replacement therapy) as judged by
- •the investigator.
- •6. 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 including known severe hypersensitivity reactions (Grade >= 3)
- •to monoclonal antibodies.
- •7. Inadequate organ function defined by the following laboratory parameters:
- •Absolute Neutrophil Count (ANC) < 1500/µl.
- •Hemoglobin (Hb) < 9 g/dl (< Hb 5.6 mmol/L), may have been transfused.
- •Platelet count < 100.000/µl.
- •Serum creatinine > 1.5 x ULN or eGFR < 60 mL/min (as per Cockroft-Gault
- •ALT or AST > 1.5 x ULN.
- •Serum total bilirubin > 1.5 x ULN.
- •8. Any medical condition requiring continuous systemic treatment with either
- •corticosteroids (> 10 mg daily prednisone equivalents) or other systemic
- •immunosuppressive medications (e.g. methotrexate, azathioprine, interferons,
- •mycophenolate, anti-TNF agents and other) within 2 weeks before consenting to
- •study participation (i.e. signing ICF) except for the following: intranasal,
- •inhaled, topical, local steroid applications/injection (e.g., intra-articular
- •injection) or single doses of systemic corticosteroids as
- •premedication/prevention for hypersensitivity reactions (e.g., CT scan
- •premedication).
- •9. 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.
- •10. Any known or suspected, current or chronic infection, immunodeficiency
- •disorder or autoimmune disease requiring systemic treatment and/or that might
- •deteriorate when receiving an immunostimulatory agent (e.g. chronic lymphocytic
- •leukemia (CLL) or allogeneic stem-cell transplantation).
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