A Phase Ib, Open-Label Trial of MOv18 IgE in Patients With Advanced Ovarian Cancer
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.
• 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.
⁃ Estimated life expectancy of \>3 months, (91 days), in the opinion of the Investigator.
⁃ Adequate haematological function, including all of the following:
⁃ i. Absolute neutrophil count (ANC) ≥1.5 × 109/L (\>1,500/mm3). G-CSF or GM-CSF may not be used to achieve this level.
⁃ ii. Platelets ≥100 × 109/L (\>100,000 per mm3) iii. Haemoglobin level \>9 g/dL obtained within 14 days before Day 1. Packed red blood cell transfusion is acceptable, if the patient has a stable result of ≥9 g/dL for at least 1 week post-transfusion. Erythropoietin should not be used to achieve this level.
⁃ iv. Adequate coagulation function at screening as determined by prothrombin time (PT) ≤1.5 × upper limit of normal (ULN) or international normalised ratio (INR) \<1.5 and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. Does not apply to patients on an anti coagulant with a stable dose within 28 days prior to first dose.
⁃ v. Lymphocyte count ≥1000 cells/mm3, (1.0x10\*9/L)
⁃ Intact immune system as demonstrated by CD4 count ≥500 cells/mm3 and CD8 count ≥150 cells/mm3.
⁃ Adequate renal function as demonstrated by creatine or measured and calculated creatinine clearance (estimated glomerular filtration rate \[eGFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\] - deduced using the Cockcroft-Gault equation: creatinine clearance: (140-age \[years\]) × weight (kg)/(serum creatinine \[mg/dL\] × 72) × 0.85 ≤1.5 × ULN, or ≥60 mL/min for a patient with creatinine levels \>1.5 × institutional ULN.
⁃ Adequate hepatic function:
⁃ i. Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for a patient with total bilirubin levels \>1.5 × ULN.
⁃ ii. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
⁃ iii. Albumin ≥3.0 g/dL.
⁃ Recovered from all chemotherapy-related toxicities to Grade ≤1 according to CTCAE v5.0, excluding alopecia (any grade) and peripheral neuropathy (Grade ≤2).
⁃ No history of significant cardiac or pulmonary dysfunction, including but not limited to interstitial pulmonary disease and chronic obstructive pulmonary disease.
⁃ No history of autoimmune disease.
⁃ Negative serum or urine pregnancy test.
⁃ Women of childbearing potential must have 2 negative pregnancy tests during Screening, the second within 24 hours prior to the first administration of MOv18 IgE (i.e., pre-dose at C1D1). This criterion does not apply to patients who have had a previous hysterectomy or bilateral oophorectomy.
⁃ Female patients of child bearing potential must agree to practice true abstinence or to use two forms of contraception, one of which must be highly effective. These forms of contraception must be used from the time of signing consent, throughout the treatment period, and for 6 months, (182 days), following the last dose of any study medication. Oral or injectable contraceptive agents cannot be the sole method of contraception.
⁃ Willing and able to comply with all protocol-specified assessments and the trial visit schedule.
⁃ Patient has been advised to take measures to avoid or minimise exposure of the skin to UV light, including sunbathing and solarium use for the duration of the trial and for 4 weeks following last administration of MOv18 IgE.