A Study of MOv18 IgE in Folate Receptor Alpha-expressing Platinum Resistant Ovarian Cancer

NCT06547840 | Recruiting Phase 1

• 1 other identifier: EPS101-10-02
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

EPS101-10-02 is a Phase Ib open label, multicentre clinical trial comprising of a Dose Escalation phase (Part 1) followed by a Dose Expansion phase (Part 2) of MOv18 IgE in patients with folate receptor alpha-expressing (5% or higher) platinum resistant ovarian cancer The dose escalation part of the study will primarily assess the safety and tolerability of MOv18 IgE in ascending dose cohorts, until the determination of the maximum tolerated dose (MTD) or maximum administered dose (MAD). Part 2 (dose expansion) will further assess the safety, tolerability and anti-tumour activity of MOv18 IgE.

Conditions

Advanced Ovarian Cancer; Platinum-resistant Ovarian Cancer

Keywords

Ovarian; Cancer; Resistant; IgE; Advanced; Platinum; Folate Receptor alpha; Antibody

Outcome Measures

Primary Outcomes (4)

• Part 1: To evaluate the safety and tolerability of MOv18 IgE

  Safety will be assessed by the incidence of AEs, SAEs and laboratory abnormalities characterized by type, incidence, and severity graded according to NCI CTCAE v5.0, seriousness, and relationship to study treatment.

  1.5 years

• Part 1: To determine the MTD or MAD of MOv18 IgE

  Determination of the highest dose level where the predicted probability of being in the excessive toxicity/overdosing interval (30%-100% toxicity) is less than 0.25, and the predicted probability of being in the target toxicity interval (20%-30% toxicity) is greater than 50%.

  1.5 years

• Part 1: To determine the recommended Part 2 expansion dose of MOv18 IgE for future dose expansion cohorts

  Establish the recommended Part 2 dose of MOv18 IgE when administered for the dose expansion phase, assessed by the incidence of AEs, SAEs and laboratory abnormalities characterized by type, incidence, and severity graded according to NCI CTCAE v5.0, seriousness, and relationship to study treatment. In addition to, pharmacokinetics and pharmacodynamics in blood or tissue.

  1.5 years

• Part 2: To make a preliminary assessment of the anti-tumour activity of MOv18 IgE at the selected dose

  Assessment of anti-tumour activity as defined by RECIST version 1.1 and/or iRECIST, in addition to Best Gynecologic Cancer InterGroup (GCIG) overall response, combining the change in CA 125 from baseline with RECIST assessment (per GCIG, 2005)

  1 year

Secondary Outcomes (3)

• Part 1: To document possible anti-tumour activity during dose escalation

  1.5 years

• Part 2: To make a preliminary assessment of the ability of MOv18 IgE at the selected dose to delay disease progression

  1 year

• Part 2: To further characterise safety and tolerability of MOv18 IgE at the selected dose

  1 year

Study Arms (1)

Part 1 and Part 2

EXPERIMENTAL

Part 1: MOv18 IgE will be administered by intravenous infusion, in dose escalation cohorts, starting at 3 mg. Part 2: MOv18 IgE will be administered by intravenous infusion at the dose determined in Part 1 Patients will receive treatment on Days 1, 8 and 15 of a 21-day cycle Patients will continue to receive study drug until disease progression, unacceptable toxicity, withdrawal of consent, death, or until the sponsor terminates the study (whichever comes first).

Drug: MOv18 IgE

Interventions

MOv18 IgE DRUG

MOv18 IgE is an anti-FRα monoclonal antibody (mAb) of the IgE class

Part 1 and Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female ≥18 years of age.
• Written (signed and dated) informed consent.
• Confirmed diagnosis by CT scan or MRI, of advanced epithelial ovarian, fallopian tube cancer, or primary peritoneal cancer with histologically- high-grade serous or endometrioid features or a predominantly serous/endometrioid component.
• Tumour tissue expressing FRα (1+, 2+ or 3+ membrane staining on at least 5% of tumour cells by immunohistochemistry using the BN3.2 antibody (Leica Biosystems).
• i. Patients must be willing to provide an archival tumour tissue block or slides, or undergo procedure to obtain a new biopsy using a low risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity ii. Note: Pre-screening for FRα expression may be performed at any point in advance of Cycle 1 Day 1
• Negative basophil activation test (BAT) prior to Cycle 1 Day 1. Note: this test may be performed in duplicate at two different sites: (i) at the treatment centre (where possible), and (ii) at a reference laboratory. Where results are discordant, (or in instances where the treatment centre is not able to perform the assay), the reference laboratory results will prevail.
• Platinum-free interval since last line of platinum of less than 6 months (182 days).
• Progressed following ≤4 prior regimens of anti-cancer therapy for ovarian cancer and no other authorised therapy is considered appropriate in the opinion of the investigator. Prior regimens can include carboplatin/paclitaxel, bevacizumab (if clinically indicated), PARP inhibitors and FRα antibody-drug conjugates.
• i. Patients who received hyperthermic intraperitoneal chemotherapy (HIPEC) or other IP therapies are eligible.
• ii. Neoadjuvant and adjuvant therapy counts as a prior regimen.
• Has measurable disease as defined by RECIST v1.1 on CT or MRI scan with at least one lesion that is accessible by image-guided biopsy and which is not a target lesion.
• i. Note: Qualification scans must be performed ≤28 days before Cycle 1 Day 1, after discontinuation of the prior regimen.
• ii. Note: Lesions previously embolised, perfused, or irradiated without objective evidence of progression before Cycle 1 Day 1 are not allowed to be considered for response assessment.
• No evidence of bowel obstruction.
• ECOG Performance Status Score 0-1 prior to Cycle 1 Day 1.

You may not qualify if:

• Non-epithelial tumour origin of the ovary, the fallopian tube, or the peritoneum (i.e., germ cell tumours).
• Ongoing malignant ascites requiring drainage \>500cc within 2 weeks prior to Day 1.
• Anorexic and unable to eat.
• Taking beta-blockers (at PI discretion) and unable to interrupt beta-blockade (which may counteract the therapeutic effects of adrenaline), or full dose 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. Treatment may be reintroduced 48 hours post dose administration.
• i. Note: Beta blockers may continue if, in the opinion of the Investigator, it would not pose additional risk to the patient ii. Note: Only applies to full dose tricyclic anti-depressants. Low dose tricyclic anti-depressants to support conditions such as peripheral neuropathy, chronic pain, or insomnia, may be permitted at PI discretion
• History of laryngeal oedema, uncontrolled or high-risk asthma, or anaphylaxis. Patients with a history of hypersensitivity to carboplatin, taxanes, or contrast media may enter the trial at the Investigator's discretion.
• History of parasitic infections, such as helminthiasis.
• Baseline elevation in serum tryptase (indicating possible mastocytosis) or a positive BAT. Tryptase normal range is 2-15 ng/mL.
• Receiving systemic anti-cancer therapy, including immunostimulatory agents (e.g., cytokine-based modality, antigen-specific peptide immunotherapy, immune checkpoint blockade, co-stimulatory agonists) within 28 days of Cycle 1 Day 1.
• Administration of other simultaneous chemotherapy drugs, anti-cancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy and denosumab is permitted).
• Receiving radiation therapy within 14 days prior to Day 1. Local palliative radiotherapy is permitted; however, if the radiotherapy is to a target lesion, that lesion must be excluded from tumour response assessments.
• Chronic treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone (\>10 mg), cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents) within 14 days prior to Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.
• Administration of a live, attenuated vaccine within 28 days prior to Day 1 or anticipation that such a live attenuated vaccine will be required during the trial or within 5 months, (152 days), after the last dose of MOv18 IgE. Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccination. COVID vaccination is permitted as necessitated.
• Previous allogeneic bone marrow transplant or previous solid organ transplantation.
• Historical positive serology test for human immunodeficiency virus (HIV).

Sponsors & Collaborators

• Epsilogen Ltd: lead

Study Sites (7)

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

RECRUITING

Edinburgh Cancer Research Centre

Edinburgh, EH4 2XR, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7LP, United Kingdom

RECRUITING

Cambridge University - Addenbrooke's Hospital

London, CB2 0QQ, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 3SS, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6HU, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• Rebecca Kristeleit, MD

  Guy's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Epsilogen Clinical Trials

CONTACT

+44 (0) 203 657 7612; info@epsilogen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Bayesian logistic regression model with overdose control

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 9, 2024
• Study Start: September 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-06

Locations

GB (7)