Phase I Study of MOv18 IgE
Condition: Human Cancers
Intervention: MOv18 IgE; MOv18 IgE; MOv18 IgE; MOv18 IgE; MOv18 IgE; MOv18 IgE; MOv18 IgE
Intervention description: The allocated dose of 70 µg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 6 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE. Each IV infusion will be preceded by an intradermal injection of 0.1 mL of a 2 µg/mL MOv18 IgE solution for safety assessment.; The allocated dose of 250 µg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 6 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE. Each IV infusion will be preceded by either an intradermal injection of 0.1 mL of a 2 µg/mL MOv18 IgE solution or a skin prick test with 2 µg/mL MOv18 IgE solution, for safety assessment.; The allocated dose of 500 µg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 6 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE. Each IV infusion will be preceded by a skin prick test with 2 µg/mL MOv18 IgE solution, for safety assessment.; The allocated dose of 700 µg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 6 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE. Each IV infusion will be preceded by a skin prick test with 2 µg/mL MOv18 IgE solution, for safety assessment.; The allocated dose of 1.5 mg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 6 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE. Each IV infusion will be preceded by a skin prick test with 2 µg/mL MOv18 IgE solution, for safety assessment.; The allocated dose of 3 mg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 6 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE. Each IV infusion will be preceded by a skin prick test with 2 µg/mL MOv18 IgE solution, for safety assessment.; Cycle 1 - The allocated dose of 6 mg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 3 weeks.
Cycle 2 - The allocated dose of 12 mg MOv18 IgE will be diluted in 250 mL saline and administered by IV infusion once weekly for 3 weeks, followed by fortnightly for 6 weeks if the patient appears to be benefiting from MOv18 IgE.
Each IV infusion will be preceded by a skin prick test with 2 µg/mL MOv18 IgE solution, for safety assessment.
Intervention MeSH terms: Immunoglobulin E
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: IgE antibody; Folate receptor; Cancer Immunotherapy; First in class

Summary:

      This first in human study of the new therapeutic antibody MOv18 immunoglobulin (Ig) E, which
      targets a protein called folate receptor alpha (FRa), 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.
    

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 of 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.