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

NCT02194426 | Completed Phase 1

• 2 other identifiers: MP0250-CP1012014-000366-21
• Study Type: interventional
• Target: 58
• Locations: 3 countries
• Sites: 4

Brief 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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (2)

• 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

Study Arms (1)

MP0250

EXPERIMENTAL

see section "intervention description" below

Drug: MP0250

Interventions

MP0250 DRUG

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

MP0250

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Molecular Partners AG: lead

Study Sites (4)

Study Site Barcelona

Barcelona, Catalonia, Spain

Location

Study Site St. Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Location

Study Site Cambridge

Cambridge, Cambridgeshire, United Kingdom

Location

Study Site Oxford

Oxford, Oxfordshire, United Kingdom

Location

Related Publications (1)

• Baird RD, Linossi C, Middleton M, Lord S, Harris A, Rodon J, Zitt C, Fiedler U, Dawson KM, Leupin N, Stumpp MT, Harstrick A, Azaro A, Fischer S, Omlin A. First-in-Human Phase I Study of MP0250, a First-in-Class DARPin Drug Candidate Targeting VEGF and HGF, in Patients With Advanced Solid Tumors. J Clin Oncol. 2021 Jan 10;39(2):145-154. doi: 10.1200/JCO.20.00596. Epub 2020 Dec 10.

  PMID: 33301375 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

MP0250

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: July 18, 2014
• Study Start: July 1, 2014
• Primary Completion: February 20, 2018
• Study Completion: February 20, 2018
• Last Updated: August 7, 2019

Record last verified: 2018-04

Locations

GB (2); CH (1); ES (1)