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

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: MP0250

• Registration Number: NCT02194426
• Lead Sponsor: Molecular Partners AG

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-06-12
• Study Start: 2014-07
• Study First Submitted QC: 2014-07-15
• Study First Posted: 2014-07-18
• Primary Completion: 2018-02-20
• Study Completion: 2018-02-20
• Status Verified: 2018-04
• Last Update Submitted: 2019-08-06
• Last Update Posted: 2019-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MP0250	MP0250	see section "intervention description" below

Primary Outcome Measures

Name	Time	Method
Frequency of adverse events	From inclusion up to week 56
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
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

Name	Time	Method
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

Trial Locations

Locations (4)

Study Site St. Gallen; 🇨🇭 St. Gallen, Saint Gallen, Switzerland

Study Site Oxford; 🇬🇧 Oxford, Oxfordshire, United Kingdom

Study Site Cambridge; 🇬🇧 Cambridge, Cambridgeshire, United Kingdom

Study Site Barcelona; 🇪🇸 Barcelona, Catalunya, Spain