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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02194426
• Other study ID #: MP0250-CP101
• Secondary ID: 2014-000366-21
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2014
• Est. completion date: February 20, 2018

Study information

• Verified date: April 2018
• Source: Molecular Partners AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: February 20, 2018
• Est. primary completion date: February 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female = 18 years

2. 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

3. Progressive or stable disease documented radiologically in the 4 weeks prior to screening

4. Presence of a measurable tumour or a tumour evaluable per RECIST v1.1

5. ECOG performance status = 1

6. Life expectancy = 12 weeks

7. 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

8. 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)

9. 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

10. Female patients with a negative pregnancy test result at screening and baseline

Exclusion Criteria:

1. Female patients pregnant or breast-feeding

2. Haematological malignancies or other secondary malignancy, that is currently clinically significant or requires active intervention

3. Known untreated or symptomatic brain metastases

4. Predominantly squamous non-small cell lung carcinoma

5. 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

6. 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

7. 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

8. Exclusion criterion removed

9. 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

10. Serious non-healing wound, active ulcer or untreated bone fracture

11. Proteinuria at screening as defined by = 1+ on urinalysis dipstick, confirmed by = 1g in 24h urinalysis

12. Uncontrolled hypertension or any other serious cardiovascular or cardiac condition as judged by the investigator

13. Severe or uncontrolled renal insufficiency

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• MP0250
Intravenous application by infusion of MP0250 at up to six dose levels, every other week for up to 24 infusions.

Locations

Country	Name	City	State
Spain	Study Site Barcelona	Barcelona	Catalunya
Switzerland	Study Site St. Gallen	St. Gallen	Saint Gallen
United Kingdom	Study Site Cambridge	Cambridge	Cambridgeshire
United Kingdom	Study Site Oxford	Oxford	Oxfordshire

Sponsors (1)

Lead Sponsor	Collaborator
Molecular Partners AG

Countries where clinical trial is conducted

Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with dose limiting toxicities		From the Day 0 (first infusion) up to 35 days
Primary	Vital signs		From inclusion (week -4) up to week 56
Primary	Frequency of adverse events		From inclusion up to week 56
Primary	MP0250 plasma concentration-time profile		From Day 0 (first infusion) up to week 56
Primary	Nature of dose limiting toxicities		From the Day 0 (first infusion) up to 35 days
Primary	Nature of adverse events		From inclusion up to week 56
Primary	Severity of adverse events		From inclusion up to week 56
Primary	Blood chemistry values		From inclusion (week -4) up to week 56
Primary	Haematology values		From inclusion (week -4) up to week 56
Primary	Urine values		From inclusion (week -4) up to week 56
Primary	Electrocardiogram measurements		From inclusion (week -4) up to week 56
Primary	Pharmacokinetics parameters		From Day 0 (first infusion) up to week 56
Secondary	Incidence of anti-drug-antibodies		From the Day 0 (first infusion) up to week 56
Secondary	Titre of anti-drug-antibodies		From the Day 0 (first infusion) up to week 56