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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: MP0250

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain
      • Study Site Barcelona
• Switzerland
  • Saint Gallen
    • St. Gallen, Saint Gallen, Switzerland
      • Study Site St. Gallen
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom
      • Study Site Cambridge
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom
      • Study Site Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Molecular Partners AG

Publications and helpful links

General Publications

• Baird RD, Linossi C, Middleton M, Lord S, Harris A, Rodón 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): February 20, 2018
• Study Completion (Actual): February 20, 2018

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: July 15, 2014
• First Posted (Estimate): July 18, 2014

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: August 6, 2019
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: MP0250-CP101; 2014-000366-21 (EudraCT Number)