AzTrials
AzTrials

NeoplasmsPhase 1NCT03084926

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

A Phase 1 study testing MP0274 in people with Neoplasms, run by Molecular Partners AG at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
MP0274
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
4 sitesin 3 countries
Study dates
8 Aug 2017to 13 Dec 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 28Show fewer
  • 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:
  • Serum creatinine ≤ 1.5 mg/dL Or
  • Serum creatinine clearance ≥ 40 mL/min (by Cockcroft-Gault equation)
  • Values for potassium, calcium and magnesium must be within normal ranges. Patients may receive supplements to meet these requirements
  • Adequate hepatic function
  • Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5 × ULN, or if known hepatic metastases ≤5 × ULN
  • Total bilirubin ≤ 1.5 × ULN
  • Serum albumin concentration ≥ 30 g/L
  • Highly effective contraception, for both women and men, is ensured:
  • Female patients must be either post-menopausal women, or highly effective contraceptive measures must be ensured. Menopause is defined as occurring 12 months after last menstrual period
  • Pre-menopausal or menopausal women who fulfill the following conditions: They must have had a prior hysterectomy or be using 2 highly effective methods of contraception (i.e. with failure rates less than 1% per year when used consistently and correctly, e.g. established use of oral, injected or implanted hormonal methods of contraception; intrauterine device; condom with spermicidal foam or gel or film or cream or suppository), from the time of screening through the whole treatment phase of the study, and for at least 3 months following the completion of the last MP0274 administration
  • Men capable of fathering a child must agree to use barrier contraception (combination of a condom and spermicide) or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, during the treatment phase of the study and for at least 3 months following the completion of the last MP0274 infusion
  • Men capable of fathering a child must refrain from donating sperm for duration of study and for at least 4 months after last administration of MP0274
  • Female patients of child-bearing potential must have a negative serum pregnancy test result at screening

Who cannot join

  • 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
Show all 40Show fewer
  • 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
  • Any of the following cardiac exclusion criteria:
  • Known history of symptomatic congestive heart failure
  • LVEF < 55%, assessed by 2-dimensional echocardiography (2D Echo)
  • Known absolute decrease in LVEF of ≥ 15 absolute percentage points on prior anti-HER2 therapy, even if asymptomatic
  • High-risk uncontrolled arrhythmias such as resting bradycardia with a heart rate < 55 beat/min, atrial tachycardia with a resting heart rate > 100 beats/min, clinically significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular (AV) block (second degree AV-block Type 2 or third degree AV-block), implantable pacemaker or defibrillator, family history of long QT syndrome
  • QTc prolongation > Grade 1 (> 480 ms) at screening measured on 2 separate ECGs at least 10 min apart
  • Angina pectoris requiring anti-angina medication
  • History of cardiac infarction or evidence of transmural infarction on ECG
  • Troponin ≥ Grade 1 (above the upper limit of normal)
  • Both, CK > 2.5-fold ULN range and CK-MB > 6% of total CK at screening
  • Coronary artery bypass graft, coronary artery angioplasty or stent placement within 12 months before screening
  • Clinically significant valvular heart disease
  • Known hyperthyroidism
  • Hypertension which is not controlled to systolic < 160 mm Hg and diastolic < 100 mm Hg
  • Clinically significant lung disorders such as:
  • Non-malignant interstitial lung disease or pneumonitis
  • Dyspnea of any cause requiring supplemental oxygen therapy and dyspnea at rest due to complications of advanced malignancy and co-morbidities
  • History of allogeneic bone marrow or stem cell transplant
  • Known positivity for human immunodeficiency virus (HIV) or history of HIV
  • Patients having active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HbsAg] test at screening) or active hepatitis C at screening
  • o Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HbcAb] and absence of HbsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
  • Any active infection requiring the use of parenteral anti-microbial agents or that is > Grade 2
  • Unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures
  • Concurrent participation in another clinical study involving treatment with the IMP and/or safety follow-up post treatment with IMP (Long-term Survival Follow-up is permitted)
  • Previous treatment with MP0274 (to exclude re-entering the study)
  • Hypersensitivity to any of the excipients of the finished drug MP0274
  • Patients who are pregnant or breast-feeding

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

Germany2 sites

  • Study Site Frankfurt

    Frankfurt

  • Study Site Heidelberg

    Heidelberg

Other trials in Germany

Switzerland1 site

  • Study Site St. Gallen

    Sankt Gallen, Canton of St. Gallen

Other trials in Switzerland

United Kingdom1 site

  • Study Site Cambridge

    Cambridge

Other trials in United Kingdom

About this study

Official title: A Phase 1, First-in-human, Single-arm, Multi-center, Open-label, Repeated-Dose, Dose-escalation Study to Assess Safety, Tolerability and Pharmacokinetics of MP0274 in Patients With Advanced HER2-positive Solid Tumors

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
Being tested
MP0274
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MP0274Drug

    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

Study groups in NCT03084926
Study groupRoleWhat they receive
MP0274ExperimentalNot described
Receives: Drug: MP0274

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of adverse events

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

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

Secondary outcomes (3)

  1. Pharmacokinetics of MP0274

    Serum concentration-time profile of MP0274

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

  2. Preliminary assessment of anti-tumor activity of MP0274

    Efficacy evaluation based on Response Evaluation Criteria in Solid Tumors (RECIST)

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

  3. Incidence of anti-drug-antibodies

    Serum concentration-time profile of anti-drug antibodies

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2017
  2. Study start8 Aug 2017
  3. Primary completion13 Dec 2021
  4. Study completion13 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03084926
Sponsor's protocol ID
MP0274-CP101
Other IDs
2016-004712-36, 2016
Status last verified
Jan 2022
First submitted
6 Mar 2017
Last updated
10 Jan 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MP0274 in people with Neoplasms, run by Molecular Partners AG at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany, Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (time frame: from first infusion to end-of-study visit, up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03084926.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in