Clinical Trials /

Phase I Study of MOv18 IgE, a First in Class Chimeric IgE Antibody in Patients With Advanced Solid Tumours

NCT02546921

Description:

This first in human study of the new therapeutic antibody MOv18 IgE in patients with advanced cancer seeks to demonstrate the potential for the use of this IgE antibody as an example of the use of the IgE class of antibodies for the treatment of cancer.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

This First in Human Study of the New Therapeutic <span class="go-doc-concept go-doc-intervention">Antibody</span> MOv18 IgE in Patients With Advanced <span class="go-doc-concept go-doc-disease">Cancer</span>

Title

  • Brief Title: This First in Human Study of the New Therapeutic Antibody MOv18 IgE in Patients With Advanced Cancer
  • Official Title: A Cancer Research UK Phase I Study of MOv18 IgE, a First in Class Chimeric IgE Antibody Against Folate Receptor-alpha, in Patients With Advanced Solid Tumours
  • Clinical Trial IDs

    NCT ID: NCT02546921

    ORG ID: CRUKD14/001

    Trial Conditions

    Human Cancers

    Trial Interventions

    Drug Synonyms Arms
    MOv18 IgE

    Trial Purpose

    This first in human study of the new therapeutic antibody MOv18 IgE in patients with
    advanced cancer seeks to demonstrate the potential for the use of this IgE antibody as an
    example of the use of the IgE class of antibodies for the treatment of cancer.

    Detailed Description

    Therapeutic antibodies have significantly improved the prognosis of patients with a range of
    cancers. Currently available therapeutic antibodies belong to the IgG class. This study is
    looking at a new drug called MOv18 which belongs to a different class of antibody, the IgE
    class. IgE antibodies may trigger a more powerful immune response to tumour cells than these
    available IgG antibodies and so be more effective in treating certain types of cancer. This
    is the first time an IgE antibody therapy will be given to patients with cancer.

    MOv18 IgE antibodies are designed to recognise and attach to a particular protein called the
    folate receptor alpha. Scientists have found more of this protein on the surface of certain
    cancer cells than on the surface of normal cells, most commonly ovarian cancer and to a
    lesser extent cancers of the kidney, pleura, endometrium, lung, breast, bladder, colon and
    pancreas. Once attached, the MOv18 IgE antibody should trigger the body's own immune system
    to attack and kill the cancer cells.

    Patients will be selected based on the presence of folate receptor protein on their tumour
    in a previous biopsy. The study is the first study of this new antibody treatment to be
    given to humans and will focus primarily on the assessment of safety confirming the findings
    of preclinical studies that exposure to MOv18 IgE will not trigger anaphylaxis. This is in
    addition to extensive PK, biodistribution of the antibody and immunological response. The
    study will follow a dose escalation design where small groups of patients are treated at a
    set dose, starting with a very low dose followed by exponential increasing doses, to find a
    safe dose at which the drug has a good chance of effectively treating the cancer. Patients
    will receive a short course of treatment. The majority of patients treated at the higher
    dose levels will be asked to provide a pre and post treatment biopsy to explore the effect
    of the treatment on the tumour.

    Trial Arms

    Name Type Description Interventions

    Eligibility Criteria

    Inclusion Criteria:

    1. Histologically or cytologically-proven advanced, unresectable solid tumour of a type
    known to express FR in a percentage of cases

    2. Archival tumour tissue expressing FR (1+, 2+ or 3+ membrane staining on at least 5%
    of tumour cells by immunohistochemistry using the BN3.2 antibody, based on the
    technique described by Lawson & Scorer, 2010). For patients who undergo a
    pre-treatment tumour biopsy, FR expression in the pre-treatment sample takes
    precedence over results from any previous archival specimen.

    3. Advanced disease for which no alternative therapy is felt to be appropriate.

    4. Measurable disease or disease evaluable by tumour marker. Measurable disease is
    preferred for patients entering higher cohorts to facilitate efficacy assessments.

    5. World Health Organisation (WHO) performance status of 0 or 1 and a life expectancy of
    at least 12 weeks.

    6. Haematological and biochemical indices within the ranges shown below. These
    measurements should be performed within 7 days before the first dose of MOv18 IgE
    (Day -7 to Pre-dose on Day 1). Measurements performed before Day -7 may be accepted
    by the CDD to demonstrate eligibility if repeat testing is logistically difficult for
    the patient and is not considered necessary medically in the opinion of the
    Investigator or CDD.

    Laboratory Test Value required Haemoglobin (Hb) 9.0 g/dL Absolute neutrophil count
    1.5 x 10^9/L Platelet count 100 x 10^9/L Serum bilirubin 1.5 x upper limit of
    normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
    2.5 x ULN unless raised due to liver metastases in which case up to 5 x ULN is
    permissible Serum creatinine 1.5 x ULN

    7. Aged 16 years or over at the time consent is given.

    8. Written (signed and dated) informed consent and capable of co-operating with
    treatment and follow-up.

    Exclusion Criteria:

    1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or
    chemotherapy during the previous four weeks (six weeks for nitrosoureas and
    mitomycin-C) and investigational medicinal products during the previous 4 weeks, or 5
    product half-lives before treatment.

    2. Patients on beta-blockers and unable to interrupt beta-blockade (which may counteract
    the therapeutic effects of adrenaline), or tricyclic anti-depressants/MAOIs (which
    can dangerously augment the effects of adrenaline). These agents should be
    discontinued at least 4 half-lives before administration of the first dose of MOv18
    IgE and for the duration of MOv18 IgE therapy.

    3. Patients on bisphosphonates or treated with bisphosphonates in the last 18 months.

    4. Ongoing toxic manifestations of previous treatments that have not resolved to Grade 1
    or lower (other than alopecia of any grade or Grade 2 peripheral neuropathy).

    5. Known brain metastases that have not been previously treated and been stable for at
    least 2 months.

    6. Female patients who are able to become pregnant (or already pregnant or lactating).
    However, those female patients who have a negative serum or urine pregnancy test
    before enrolment and agree to use two highly effective forms of contraception (oral,
    injected or implanted hormonal contraception and condom; have an intra-uterine device
    and condom; diaphragm with spermicidal gel and condom) effective at the first
    administration of IMP, throughout the study and for six months afterwards are
    considered eligible.

    7. Male patients with partners of child-bearing potential (unless they agree to take
    measures not to father children by using one form of highly effective contraception
    at the first administration if IMP, throughout the study and for six months
    afterwards). Men with pregnant or lactating partners should be advised to use barrier
    method contraception (for example, condom plus spermicidal gel) to prevent exposure
    to the foetus or neonate.

    8. Major thoracic or abdominal surgery from which the patient has not yet recovered.

    9. At high risk from the effects of anaphylaxis because of non-malignant systemic
    disease including active uncontrolled infection, cardiac failure, peripheral vascular
    disease, previous cerebrovascular accident (CVA), dyspnoea due to heart failure,
    extensive lung metastases, significant pleural effusions or other conditions.

    10. History of laryngeal oedema, uncontrolled or high risk asthma (according to Global
    Initiative for Asthma (GINA) guidelines), or anaphylaxis.

    11. Patients with any congenital or acquired immunodeficiency syndrome or receiving
    immunosuppressive therapy (including any dose of systemic corticosteroids), or who
    are immunosuppressed post organ transplant. However, patients receiving inhaled
    corticosteroids and patients with a history of allergy (other than anaphylaxis) are
    eligible, as are patients with a history of auto-immune disease.

    12. Known to be serologically positive for hepatitis B, hepatitis C or human
    immunodeficiency virus (HIV).

    13. Patients with baseline elevation in -tryptase (indicating possible mastocytosis).

    14. Participating or planning to participate in another interventional clinical trial,
    whilst taking part in this study. Participation in an observational study or in the
    follow-up phase of a previous interventional trial is acceptable.

    15. Any other condition which in the Investigator's opinion would not make the patient a
    good candidate for the clinical study.

    Minimum Eligible Age: 16 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Reported safety information (adverse events graded for severity using the NCI CTCAE version 4.02)

    Secondary Outcome Measures

    Antitumour activity measured according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1

    Assessment of Disease Response using CA 125 Tumour Marker

    Trial Keywords

    IgE antibody

    Folate receptor

    Cancer Immunotherapy

    First in class