Clinical Trials /

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



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:



Phase 1

Trial Eligibility



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


  • Human Cancers


MOv18 IgE


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


Eligibility Criteria

        Inclusion Criteria:

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

          2. Archival tumour tissue expressing FRα (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).

          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)
             or agree to sexual abstinence*. 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.

             * Abstinence is only considered to be an acceptable method of contraception when this
             is in line with the preferred and usual lifestyle of the patient. Periodic abstinence
             (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are
             not acceptable methods of contraception.

          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. Patients with a history of
             hypersensitivity to carboplatin, taxanes, or contrast media may enter the study at the
             investigator's discretion.

         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 serum tryptase (indicating possible mastocytosis)
             or a positive baseline basophil activation test (indicating a hypothetical potential
             for anaphylaxis with MOv18 IgE).

         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.

         16. Patients unwilling or unable to interrupt antihistamines (which may interfere with
             skin prick testing). Antihistamines should be discontinued at least 4 half-lives
             before the first skin prick test.
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Reported safety information (adverse events graded for severity using the NCI CTCAE version 4.02)
Time Frame:Safety data will be collected from the time of informed consent until 56 days after the last dose of MOv18 IgE.
Safety Issue:
Description:Reported safety information in the form of adverse events graded for severity using the NCI CTCAE version 4.02 and which will be assessed by the reporting study doctors for a causal relationship to MOv18. Adverse events related to infusion with MOv18 will be categorised as being either due to IgE mediated mast cell degranulation i.e. anaphylaxis or as cytokine release syndrome.

Secondary Outcome Measures

Measure:Antitumour activity measured according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
Time Frame:Radiological disease assessment at screening/baseline and every 6 weeks to end of treatment
Safety Issue:
Measure:Assessment of Disease Response using CA 125 Tumour Marker
Time Frame:Disease response assessment at screening/baseline and every 3 weeks if clinically appropriate for tumour type to end of treatment
Safety Issue:


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cancer Research UK

Trial Keywords

  • IgE antibody
  • Folate receptor
  • Cancer Immunotherapy
  • First in class

Last Updated

December 4, 2020