Clinical trial NCT02194426: First-in-human Study to Investigate the Safety, Tolerability and Blood Levels of the Test Drug MP0250 in Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neoplasms
Lead sponsor: Molecular Partners AG
Sponsor class: INDUSTRY
First posted: 2014-07-18
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
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

Primary outcomes:
measure: Proportion of patients with dose limiting toxicities
timeFrame: From the Day 0 (first infusion) up to 35 days
measure: Vital signs
timeFrame: From inclusion (week -4) up to week 56
measure: Frequency of adverse events
timeFrame: From inclusion up to week 56
measure: MP0250 plasma concentration-time profile
timeFrame: From Day 0 (first infusion) up to week 56
measure: Nature of dose limiting toxicities
timeFrame: From the Day 0 (first infusion) up to 35 days
measure: Nature of adverse events
timeFrame: From inclusion up to week 56
measure: Severity of adverse events
timeFrame: From inclusion up to week 56
measure: Blood chemistry values
timeFrame: From inclusion (week -4) up to week 56
measure: Haematology values
timeFrame: From inclusion (week -4) up to week 56
measure: Urine values
timeFrame: From inclusion (week -4) up to week 56
measure: Electrocardiogram measurements
timeFrame: From inclusion (week -4) up to week 56
measure: Pharmacokinetics parameters
timeFrame: From Day 0 (first infusion) up to week 56
Secondary outcomes:
measure: Incidence of anti-drug-antibodies
timeFrame: From the Day 0 (first infusion) up to week 56
measure: Titre of anti-drug-antibodies
timeFrame: From the Day 0 (first infusion) up to week 56
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Study Site Barcelona
state: Catalunya
city: St. Gallen
country: Switzerland
facility: Study Site St. Gallen
state: Saint Gallen
city: Cambridge
country: United Kingdom
facility: Study Site Cambridge
state: Cambridgeshire
city: Oxford
country: United Kingdom
facility: Study Site Oxford
state: Oxfordshire
Study officials:
References:
citation: 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.