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

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ClinicalTrials.gov Identifier: NCT02546921
Recruitment Status : Recruiting
First Posted : September 11, 2015
Last Update Posted : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Human Cancers Drug: MOv18 IgE Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Primary Purpose: Treatment
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
Study Start Date : September 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: MOv18 IgE
    The allocated dose of MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for six weeks.


Primary Outcome Measures :
  1. 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. ]
    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 :
  1. 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 ]
  2. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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). 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 β-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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02546921


Contacts
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Contact: James Spicer, Dr 0207 188 4260 james.spicer@kcl.ac.uk

Locations
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United Kingdom
Addenbrooke's Hospital, Cambridge Recruiting
Cambridge, United Kingdom
Principal Investigator: Bristi Basu, Dr         
Guy's and St Thomas's Hospital Recruiting
London, United Kingdom, SE1 9RT
Contact       james.spicer@kcl.ac.uk   
Principal Investigator: James Spicer, Dr         
The Royal Marsden Hospital Recruiting
London, United Kingdom
Principal Investigator: Udai Banerji, Prof         
University College London Hospital Recruiting
London, United Kingdom
Principal Investigator: Rebecca Kristeleit, Dr         
Sponsors and Collaborators
Cancer Research UK

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Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT02546921    
Other Study ID Numbers: CRUKD14/001
First Posted: September 11, 2015    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019
Keywords provided by Cancer Research UK:
IgE antibody
Folate receptor
Cancer Immunotherapy
First in class
Additional relevant MeSH terms:
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Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs