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

NCT ID: NCT02194426

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-02-20

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MP0250

see section "intervention description" below

Group Type: EXPERIMENTAL

MP0250

Intervention Type: DRUG

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

Interventions

MP0250

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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Molecular Partners AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Study Site Barcelona

Barcelona, Catalonia, Spain

Study Site St. Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Study Site Cambridge

Cambridge, Cambridgeshire, United Kingdom

Study Site Oxford

Oxford, Oxfordshire, United Kingdom

Countries

Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33301375 (View on PubMed)

Other Identifiers

2014-000366-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MP0250-CP101

Identifier Type: -

Identifier Source: org_study_id