First-in-human Study to Investigate Safety, Blood Levels and Activity of MP0274 in Cancer Patients With HER2-positive Solid Tumors

NCT03084926 | Completed Phase 1

• 2 other identifiers: MP0274-CP1012016-004712-36
• Study Type: interventional
• Target: 22
• Locations: 3 countries
• Sites: 4

Brief Summary

This study is investigating a new experimental therapy, MP0274, a DARPin® drug candidate targeting HER2. Preclinical studies suggest that MP0274 may provide additional benefit for the treatment of HER2-positive cancers. This is the first study of MP0274 in humans and its main purpose is to test its safety and tolerability in patients with HER2-positive cancer. This study will also examine the blood levels of MP0274 at several escalating dose levels and a recommended dose for further development will be determined. The recommended dose will be tested in a second part of the study to confirm safety and to further assess the preliminary biologic and anti-tumor activity

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events

  Number and grading according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  from first infusion to end-of-study visit, up to 12 months

Secondary Outcomes (3)

• Pharmacokinetics of MP0274

  from first infusion to end-of-study visit, up to 12 months

• Preliminary assessment of anti-tumor activity of MP0274

  from first infusion to end-of-study visit, up to 12 months

• Incidence of anti-drug-antibodies

  from first infusion to end-of-study visit, up to 12 months

Study Arms (1)

MP0274

EXPERIMENTAL

Drug: MP0274

Interventions

MP0274 DRUG

Intravenous infusion of MP0274 as single agent at four planned dose levels, every three weeks until progressive disease, unacceptable toxicity or patient withdrawal for other reasons

MP0274

Eligibility Criteria

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

You may qualify if:

• Have signed and dated written informed consent prior to performing any study procedure, including screening
• Are ≥ 18 years old on the day of signing informed consent
• Have histologically confirmed and documented HER2 positive solid tumor malignancy that is unresectable, locally advanced, or metastatic with progression
• Part A of study: Assessed on tumor tissue from most recent biopsy
• Part B of study: Assessed on the latest tumor biopsy material for HER2 and other scheduled tissue testing from within 6 months before entry into the study Part A and B: Tumor tissue must be made available to the Sponsor for central testing
• Have received standard, available therapies approved for their cancer, unless they are unsuitable for these treatments (incurable disease)
• Have documented PD on most recent systemic antitumor treatment
• Disease assessment Part A: Evaluable Disease (disease that cannot be measured directly by the size of the tumor but can be evaluated by other methods) or Measurable Disease according to RECIST v1.1 (in case of skin lesions, documentation by color photography including a ruler to estimate the size of the lesion is acceptable) Part B: Measurable Disease as per RECIST 1.1
• Have an ECOG PS of 0-2
• Have adequate hematological function prior to first scheduled dose, defined as:
• Absolute neutrophil count ≥ 1500 cells/µL
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 75,000/µL
• Prothrombin time or activated partial thromboplastin (aPTT) time ≤ 1.5 × upper limit of normal (ULN)
• Adequate renal function prior to first scheduled dose, defined as either:

You may not qualify if:

• Patients will be ineligible if 1 or more of the following statements are applicable:
• Hematological malignancies or other second primary malignancy, that is currently clinically significant or requires active intervention
• Known brain metastases that are clinically unstable despite treatment with anticonvulsives and/or corticosteroids for at least 8 weeks prior to first scheduled dose of MP0274
• Receipt of any of the following previous anti-tumor treatments:
• Cumulative doxorubicin ≥ 360 mg/m2
• Cumulative epirubicin ≥ 720 mg/m2
• Lapatinib within 7 days of scheduled dosing Day 1
• Chemotherapy, trastuzumab, or trastuzumab emtansine, other biologics, targeted or experimental therapy within 4 weeks of scheduled dosing Day 1, and for pertuzumab within 12 weeks
• Nitrosoureas or mitomycin C chemotherapy within 6 weeks of scheduled dosing Day 1
• Hormonal (e.g. tamoxifen) or aromatase inhibitor therapy within 8 weeks prior to first dose MP0274, except if no change in dose or schedule 8 weeks prior to first scheduled dose MP0274
• Newly initiated therapy with bisphosphonate or receptor activator of nuclear kappa-B ligand (RANKL)-therapy within 8 weeks prior to first scheduled dose MP0274. If stable on dosing schedule for more than 8 weeks prior to first scheduled dose MP0274 these therapies are allowed. However, no new therapy with bisphosphonate/RANKL is allowed during the course of the study
• Received concurrent radiation therapy within 4 weeks prior to first scheduled dose MP0274. Local radiation therapy to painful bone metastases following institutional standard practice for palliative radiotherapy to bone metastases is allowed
• Presence of neuropathy as residual toxicity after prior anti-tumor therapy Grade \> 2
• Known history of symptomatic congestive heart failure
• LVEF \< 55%, assessed by 2-dimensional echocardiography (2D Echo)

Sponsors & Collaborators

• Molecular Partners AG: lead

Study Sites (4)

Study Site Frankfurt

Frankfurt, Germany

Location

Study Site Heidelberg

Heidelberg, Germany

Location

Study Site St. Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Location

Study Site Cambridge

Cambridge, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

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: March 6, 2017
• First Posted: March 21, 2017
• Study Start: August 8, 2017
• Primary Completion: December 13, 2021
• Study Completion: December 13, 2021
• Last Updated: January 10, 2022

Record last verified: 2022-01

Locations

CH (1); GB (1); DE (2)