Human CancersPhase 1NCT02546921
Phase I Study of MOv18 IgE
A Phase 1 study testing MOv18 IgE in people with Human Cancers, run by Cancer Research UK at 4 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Human Cancers
- What is being tested?
- MOv18 IgE
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 16 Feb 2016to 30 Jul 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically or cytologically-proven advanced, unresectable solid tumour of a type known to express FRα in a percentage of cases
- 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).
- Advanced disease for which no alternative therapy is felt to be appropriate.
- Measurable disease or disease evaluable by tumour marker. Measurable disease is preferred for patients entering higher cohorts to facilitate efficacy assessments.
- World Health Organisation (WHO) performance status of 0 or 1 and a life expectancy of at least 12 weeks.
- 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.
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- 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
- Aged 16 years or over at the time consent is given.
- Written (signed and dated) informed consent and capable of co-operating with treatment and follow-up.
Who cannot join
- 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.
- 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.
- Patients on bisphosphonates or treated with bisphosphonates in the last 18 months.
- 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).
- Known brain metastases that have not been previously treated and been stable for at least 2 months.
- 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.
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- 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.
- Major thoracic or abdominal surgery from which the patient has not yet recovered.
- 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.
- 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.
- 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.
- Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
- 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).
- 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.
- Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.
- 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.
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Addenbrooke's Hospital, Cambridge
Cambridge
Guy's and St Thomas's Hospital
London, SE1 9RT
University College London Hospital
London
Royal Marsden Hospital
Sutton, SM2 5PT
About this study
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
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.
Read the 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 IgE 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.
The MOv18 IgE antibody is designed to recognise and attach to FRa. 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 but also cancers of the kidney, 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 FRa 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 pharmacokinetic (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. 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.
- Conditions
- Human Cancers
- Being tested
- MOv18 IgE
- Keywords
- IgE antibody, Folate receptor, Cancer Immunotherapy, First in class
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MOv18 IgEDrug
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.
MOv18 IgEDrug
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.
MOv18 IgEDrug
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.
MOv18 IgEDrug
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.
MOv18 IgEDrug
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.
MOv18 IgEDrug
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.
MOv18 IgEDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| MOv18 IgE Cohort 1 | Experimental | Not described Receives: Drug: MOv18 IgE |
| MOv18 IgE Cohort 2 | Experimental | Not described Receives: Drug: MOv18 IgE |
| MOv18 IgE Cohort 3 | Experimental | Not described Receives: Drug: MOv18 IgE |
| MOv18 IgE Cohort 4 | Experimental | Not described Receives: Drug: MOv18 IgE |
| MOv18 IgE Cohort 5 | Experimental | Not described Receives: Drug: MOv18 IgE |
| MOv18 IgE Cohort 6 | Experimental | Not described Receives: Drug: MOv18 IgE |
| MOv18 IgE Cohort 7 | Experimental | Not described Receives: Drug: MOv18 IgE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs) Considered to be at Least Possibly Related to MOv18 IgE
Reported safety information in the form of AEs, categorised according to Medical Dictionary for Regulatory Activities (MedDRA) version (v) 24.0 and graded for severity according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.02. AEs will be assessed by the reporting study doctors for a causal relationship to MOv18 IgE. Count of AEs by arm.
Measured: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
DLTs graded for severity using the NCI CTCAE v4.02, measured by count of participants per arm. Two DLTs were reported; however, following review of the data, it was determined that events of this nature did not constitute DLTs. The trial protocol was updated so that if further similar events occurred then would not be considered as DLTs but the events already reported remain categorised as DLTs.
Measured: From first dose onwards until completion of Cycle 1 (3 weeks).
Number of Dose Independent Significant Toxicities
AEs judged to be due to systemic mast cell degranulation (i.e. anaphylaxis). No dose independent significant toxicities were reported. However, one event of anaphylactic reaction was classified as a DLT at the time of occurrence but, following review of the data, the trial protocol was updated. This meant that any future events of anaphylaxis would have been classified as dose independent toxicities, but the event already reported remained as a DLT.
Measured: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).
Number of Participants With Grade ≥2 Laboratory Parameter AEs Reported
Reported safety information in the form of haematological or biochemical abnormalities that were reported as AEs and graded for severity according to NCI CTCAE v4.02.
Measured: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).
Secondary outcomes (9)
Antitumour Activity (Best Response) of MOv18 IgE Measured According to the Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1
Best radiological response observed according to RECIST v1.1, presented per arm by count of participants. RECIST responses include complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). For a response to be defined as SD, the criteria must have been met at least once at a minimum interval of 6 weeks after study entry.
Measured: Radiological disease response assessment at screening/baseline and every 6 weeks to end of treatment, a median of 56.5 days (range: 38 to 124 days).
Antitumour Activity Measured by the Percentage Change in Cancer Antigen 125 (CA125) Tumour Marker Levels During the Trial, in Participants With Elevated CA125 at Baseline
The percentage change in CA125 levels from baseline to the last measurement taken on-treatment, presented as a median (minimum, maximum) for each arm.
Measured: Disease response assessment at screening/baseline and every six weeks, if clinically appropriate for tumour type, to end of treatment, for a median of 34 days (range: 5 to 91 days).
Measurement of Pharmacokinetic (PK) Parameter Area Under the Concentration-Time Curve From Time 0 to 24 Hours of MOv18 IgE
Area under the serum concentration-time curve from time 0 to 24 hours after IV MOv18 IgE administration, evaluated using an enzyme linked immunosorbent assay (ELISA) method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 within 24 hours (h) predose, then 30 mins postdose and 2, 4, 6 and 24 h postdose. Cohort 7 only (intrapatient dose escalation): Cycle 2 Day 1 predose, then 30 mins postdose and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of PK Parameter Maximum Observed Serum Concentration (Cmax) of MOv18 IgE
Cmax in serum following IV MOv18 IgE administration was analysed using an ELISA method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of PK Parameter Time to Reach Maximum Observed Serum Concentration (Tmax) of MOv18 IgE
Serum samples were analysed to determine the Tmax of MOv18 IgE following IV administration using an ELISA method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of PK Parameter Terminal Half Life for MOv18 IgE
Serum samples were analysed to determine the concentrations of MOv18 IgE using a previously developed ELISA method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of the PK Parameter Mean Residence Time (MRT) of MOv18 IgE
Serum samples were analysed to determine the MRT of MOv18 IgE following IV administration, using an ELISA method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of the PK Parameter Total Body Clearance (CLT) of MOv18 IgE
Serum samples were analysed to determine the CLT of MOv18 IgE following IV administration, using an ELISA method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of the PK Parameter Volume of Distribution (Vss) of MOv18 IgE
Serum samples were analysed to determine the Vss of MOv18 IgE following IV administration, using an ELISA method. Not all participants were analysed at all time points.
Measured: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2015 (estimated)
- Study start16 Feb 2016
- Primary completion22 Jun 2021
- Study completion30 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Human CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James Spicer, Dr, Principal investigator, Guy's and St Thomas's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02546921
- Sponsor's protocol ID
- CRUKD/14/001
- Other IDs
- 2014-000070-19, 2014
- Status last verified
- Jul 2022
- First submitted
- 19 Aug 2015
- Last updated
- 5 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stavraka C, Chauhan J, Crescioli S, McSweeney SM, Pope A, Gillett C, Di Meo A, Prassas I, Laddach R, Stoker K, McCraw AJ, Adams R, Tull TJ, Naban N, Willsmore Z, Semkova KV, Grattan CEH, McGrath J, Till SJ, Corrigan CJ, Kristeleit R, Tsoka S, Diamandis EP, Lacy KE, Pinder S, Josephs DH, Spicer J, Bax HJ, Karagiannis SN. Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha. Allergy. 2025 Aug;80(8):2225-2239. doi: 10.1111/all.16514. Epub 2025 Mar 6.
PubMed 40045925Bax HJ, Chauhan J, McCraw AJ, Grandits M, Stavraka C, Lentfer H, Hillyer T, Carroll S, Vigor K, Selkirk C, Figini M, Cheeseman J, Urbanowicz PA, Gardner RA, Spencer DIR, Westwood N, Mellor S, Spicer J, Josephs DH, Karagiannis SN. Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production. MAbs. 2025 Dec;17(1):2451295. doi: 10.1080/19420862.2025.2451295. Epub 2025 Jan 20.
PubMed 39833133Spicer J, Basu B, Montes A, Banerji U, Kristeleit R, Miller R, Veal GJ, Corrigan CJ, Till SJ, Figini M, Canevari S, Barton C, Jones P, Mellor S, Carroll S, Selkirk C, Nintos G, Kwatra V, Funingana IG, Doherty G, Gould HJ, Pellizzari G, Nakamura M, Ilieva KM, Khiabany A, Stavraka C, Chauhan J, Gillett C, Pinder S, Bax HJ, Josephs DH, Karagiannis SN. Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial. Nat Commun. 2023 Jul 25;14(1):4180. doi: 10.1038/s41467-023-39679-9.
PubMed 37491373
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02546921
- Acronym / sponsor ID
- CRUKD/14/001
- Conditions
- Human Cancers
- Keywords
- IgE antibody, Folate receptor, Cancer Immunotherapy, First in class
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- 16 Feb 2016 (actual)
- Primary completion
- 22 Jun 2021 (actual)
- Study completion
- 30 Jul 2021 (actual)
- First posted
- 11 Sep 2015 (estimated)
- Results
- Posted 5 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 IgE 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.
The MOv18 IgE antibody is designed to recognise and attach to FRa. 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 but also cancers of the kidney, 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 FRa 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 pharmacokinetic (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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| MOv18 IgE Cohort 1 | Experimental | Drug: MOv18 IgE |
| MOv18 IgE Cohort 2 | Experimental | Drug: MOv18 IgE |
| MOv18 IgE Cohort 3 | Experimental | Drug: MOv18 IgE |
| MOv18 IgE Cohort 4 | Experimental | Drug: MOv18 IgE |
| MOv18 IgE Cohort 5 | Experimental | Drug: MOv18 IgE |
| MOv18 IgE Cohort 6 | Experimental | Drug: MOv18 IgE |
| MOv18 IgE Cohort 7 | Experimental | Drug: MOv18 IgE |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically-proven advanced, unresectable solid tumour of a type known to express FRα in a percentage of cases
- 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).
- Advanced disease for which no alternative therapy is felt to be appropriate.
- Measurable disease or disease evaluable by tumour marker. Measurable disease is preferred for patients entering higher cohorts to facilitate efficacy assessments.
- World Health Organisation (WHO) performance status of 0 or 1 and a life expectancy of at least 12 weeks.
Key exclusion criteria (17 listed)
- 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.
- 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.
- Patients on bisphosphonates or treated with bisphosphonates in the last 18 months.
- 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).
- Known brain metastases that have not been previously treated and been stable for at least 2 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MOv18 IgEThe 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. | Drug | MOv18 IgE Cohort 1 |
| MOv18 IgEThe 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. | Drug | MOv18 IgE Cohort 2 |
| MOv18 IgEThe 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. | Drug | MOv18 IgE Cohort 3 |
| MOv18 IgEThe 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. | Drug | MOv18 IgE Cohort 4 |
| MOv18 IgEThe 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. | Drug | MOv18 IgE Cohort 5 |
| MOv18 IgEThe 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. | Drug | MOv18 IgE Cohort 6 |
| MOv18 IgECycle 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. | Drug | MOv18 IgE Cohort 7 |
Primary outcome
Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs) Considered to be at Least Possibly Related to MOv18 IgE
Time frame: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).
Reported safety information in the form of AEs, categorised according to Medical Dictionary for Regulatory Activities (MedDRA) version (v) 24.0 and graded for severity according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.02. AEs will be assessed by the reporting study doctors for a causal relationship to MOv18 IgE. Count of AEs by arm.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Time frame: From first dose onwards until completion of Cycle 1 (3 weeks).
DLTs graded for severity using the NCI CTCAE v4.02, measured by count of participants per arm. Two DLTs were reported; however, following review of the data, it was determined that events of this nature did not constitute DLTs. The trial protocol was updated so that if further similar events occurred then would not be considered as DLTs but the events already reported remain categorised as DLTs.
Number of Dose Independent Significant Toxicities
Time frame: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).
AEs judged to be due to systemic mast cell degranulation (i.e. anaphylaxis). No dose independent significant toxicities were reported. However, one event of anaphylactic reaction was classified as a DLT at the time of occurrence but, following review of the data, the trial protocol was updated. This meant that any future events of anaphylaxis would have been classified as dose independent toxicities, but the event already reported remained as a DLT.
Number of Participants With Grade ≥2 Laboratory Parameter AEs Reported
Time frame: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).
Reported safety information in the form of haematological or biochemical abnormalities that were reported as AEs and graded for severity according to NCI CTCAE v4.02.
9 secondary outcomes
Antitumour Activity (Best Response) of MOv18 IgE Measured According to the Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1
Time frame: Radiological disease response assessment at screening/baseline and every 6 weeks to end of treatment, a median of 56.5 days (range: 38 to 124 days).
Antitumour Activity Measured by the Percentage Change in Cancer Antigen 125 (CA125) Tumour Marker Levels During the Trial, in Participants With Elevated CA125 at Baseline
Time frame: Disease response assessment at screening/baseline and every six weeks, if clinically appropriate for tumour type, to end of treatment, for a median of 34 days (range: 5 to 91 days).
Measurement of Pharmacokinetic (PK) Parameter Area Under the Concentration-Time Curve From Time 0 to 24 Hours of MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 within 24 hours (h) predose, then 30 mins postdose and 2, 4, 6 and 24 h postdose. Cohort 7 only (intrapatient dose escalation): Cycle 2 Day 1 predose, then 30 mins postdose and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of PK Parameter Maximum Observed Serum Concentration (Cmax) of MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of PK Parameter Time to Reach Maximum Observed Serum Concentration (Tmax) of MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of PK Parameter Terminal Half Life for MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of the PK Parameter Mean Residence Time (MRT) of MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of the PK Parameter Total Body Clearance (CLT) of MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Measurement of the PK Parameter Volume of Distribution (Vss) of MOv18 IgE
Time frame: Cohorts 1-7: Cycle 1 Day 1 <24 h predose, then 30 mins postdose and 2, 4, 6, 24 and 48 h postdose; Cycle 1 Day 8 predose. Cohort 7 only (intrapatient escalation): Cycle 2 Day 1 predose, then 30 mins and 2, 4, 6 and 24 h postdose. Each cycle = 21 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40045925Stavraka C, Chauhan J, Crescioli S, McSweeney SM, Pope A, Gillett C, Di Meo A, Prassas I, Laddach R, Stoker K, McCraw AJ, Adams R, Tull TJ, Naban N, Willsmore Z, Semkova KV, Grattan CEH, McGrath J, Till SJ, Corrigan CJ, Kristeleit R, Tsoka S, Diamandis EP, Lacy KE, Pinder S, Josephs DH, Spicer J, Bax HJ, Karagiannis SN. Non-Allergic Urticarial Skin Reactions Associated With MOv18 IgE, a First-In-Class IgE Antibody Recognising Folate Receptor Alpha. Allergy. 2025 Aug;80(8):2225-2239. doi: 10.1111/all.16514. Epub 2025 Mar 6.
- Derived from this study: PubMed 39833133Bax HJ, Chauhan J, McCraw AJ, Grandits M, Stavraka C, Lentfer H, Hillyer T, Carroll S, Vigor K, Selkirk C, Figini M, Cheeseman J, Urbanowicz PA, Gardner RA, Spencer DIR, Westwood N, Mellor S, Spicer J, Josephs DH, Karagiannis SN. Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production. MAbs. 2025 Dec;17(1):2451295. doi: 10.1080/19420862.2025.2451295. Epub 2025 Jan 20.
- Derived from this study: PubMed 37491373Spicer J, Basu B, Montes A, Banerji U, Kristeleit R, Miller R, Veal GJ, Corrigan CJ, Till SJ, Figini M, Canevari S, Barton C, Jones P, Mellor S, Carroll S, Selkirk C, Nintos G, Kwatra V, Funingana IG, Doherty G, Gould HJ, Pellizzari G, Nakamura M, Ilieva KM, Khiabany A, Stavraka C, Chauhan J, Gillett C, Pinder S, Bax HJ, Josephs DH, Karagiannis SN. Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial. Nat Commun. 2023 Jul 25;14(1):4180. doi: 10.1038/s41467-023-39679-9.
- Simple summary of trial on Cancer Research UK Trial DatabaseLink provided by the sponsor.
- Interim phase 1 data evaluating MOv18 IgE, an anti-folate receptor alpha IgE antibody, in cancer patients with advanced solid tumours presented at the AACR Virtual Annual Meeting ILink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Spicer, Dr principal investigator
Guy's and St Thomas's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MOv18 IgE in people with Human Cancers, run by Cancer Research UK at 4 sites in United Kingdom.
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 9 inclusion and 17 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 5 Jun 2023. 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 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?
Yes. Results are posted in the registry (first posted 5 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs) Considered to be at Least Possibly Related to MOv18 IgE (time frame: From the date of written informed consent and until the end of safety follow up period for MOv18 IgE, a median of 88.5 days (range: 13 to 181 days).). The study lists 4 primary outcomes in all. 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 NCT02546921, which also lists 3 linked publications.
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 5 Jun 2023.