First-in-human Study to Investigate the Safety, Tolerability and Blood Levels of the Test Drug MP0250 in Cancer Patients

Study Overview
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Brief Summary
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This research study is looking at a new DARPin® drug candidate, called MP0250. There is evidence from preclinical studies that MP0250 may be effective in the treatment of cancer. This is the first study of MP0250 in humans and its main purpose is to test its safety and tolerability in patients with cancer. This study will also examine how the drug is changed by and removed from the body and look for indicators that the drug may be effective against cancer. This study will test several different dose levels of the study drug to determine the safety and tolerability profile of the drug.

Official Title
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A Phase I Multi-centre, Open-label, Repeated-dose, Dose-escalation Study to Assess Safety, Tolerability and Pharmacokinetics of MP0250 in Patients With Advanced Solid Tumours

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: MP0250


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years Histologically confirmed and documented advanced or metastatic solid tumour refractory to at least 1 prior regimen of standard treatment or for which no curative therapy is available and for whom MP0250 is a reasonable option Progressive or stable disease documented radiologically in the 4 weeks prior to screening Presence of a measurable tumour or a tumour evaluable per RECIST v1.1 ECOG performance status ≤ 1 Life expectancy ≥ 12 weeks Adequate haematological function prior to first dose, defined as: Absolute neutrophils count ≥ 1500 cells/μL Haemoglobin ≥ 9 g/dL Platelet count > 100,000/μL Prothrombin time or partial thromboplastin time < 1.2 x ULN Adequate renal function prior to first dose, defined as either Serum creatinine < 1.5 mg/dL or Serum creatinine clearance ≥ 50 mL/min/m2 (by Cockroft-Gault equation) Adequate hepatic function prior to first dose, defined as Total bilirubin ≤ 1.5 x ULN AST/ALT ≤ 2.5 x ULN, or ≤ 5 x ULN if known hepatic metastases Alkaline phosphatase ≤ 2.5 x ULN, or ≤ 5 x ULN if known hepatic or bone metastases Female patients with a negative pregnancy test result at screening and baseline Exclusion Criteria: Female patients pregnant or breast-feeding Haematological malignancies or other secondary malignancy, that is currently clinically significant or requires active intervention Known untreated or symptomatic brain metastases Predominantly squamous non-small cell lung carcinoma Anti-tumour treatment within 4 weeks of the first infusion of MP0250, such as chemotherapy, experimental or targeted therapy, biologics, hormonal therapy and radiotherapy. The anti-tumour treatments below need longer wash-out periods and must not be given within the indicated weeks of the first infusion of MP0250: i. Nitrosoureas: 6 weeks ii. Monoclonal antibodies: 8 weeks Exceptions: the following anti-tumour treatments are allowed as indicated i. Palliative radiation to bone metastases to relieve bone pain ii. Standard of care treatment such as bone modifying agents (i.e. bisphosphonates), denosumab, maintenance hormonal therapy for metastatic prostate and breast cancers, hormone-replacement therapy, and oral contraceptives Presence of residual toxicities of CTC-AE Grade ≥ 2 after prior anti-tumour therapy at screening. Except meeting other exclusion criteria, grade 1 toxicities related to previous treatments are acceptable at the time of the first infusion of MP0250, as well as Grade 2 alopecia Exclusion criterion removed Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks of first dose or anticipation of major surgical procedure during the course of the study, core biopsy or minor surgical procedures within 1 week of first dose Serious non-healing wound, active ulcer or untreated bone fracture Proteinuria at screening as defined by ≥ 1+ on urinalysis dipstick, confirmed by ≥ 1g in 24h urinalysis Uncontrolled hypertension or any other serious cardiovascular or cardiac condition as judged by the investigator Severe or uncontrolled renal insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP0250<br>see section intervention description below | Drug: MP0250<br>* Intravenous application by infusion of MP0250 at up to six dose levels, every other week for up to 24 infusions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with dose limiting toxicities |  | From the Day 0 (first infusion) up to 35 days | 
| Vital signs |  | From inclusion (week -4) up to week 56 | 
| Frequency of adverse events |  | From inclusion up to week 56 | 
| MP0250 plasma concentration-time profile |  | From Day 0 (first infusion) up to week 56 | 
| Nature of dose limiting toxicities |  | From the Day 0 (first infusion) up to 35 days | 
| Nature of adverse events |  | From inclusion up to week 56 | 
| Severity of adverse events |  | From inclusion up to week 56 | 
| Blood chemistry values |  | From inclusion (week -4) up to week 56 | 
| Haematology values |  | From inclusion (week -4) up to week 56 | 
| Urine values |  | From inclusion (week -4) up to week 56 | 
| Electrocardiogram measurements |  | From inclusion (week -4) up to week 56 | 
| Pharmacokinetics parameters |  | From Day 0 (first infusion) up to week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-drug-antibodies |  | From the Day 0 (first infusion) up to week 56 | 
| Titre of anti-drug-antibodies |  | From the Day 0 (first infusion) up to week 56 |