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

Inclusion Criteria:

1. Female ≥18 years of age.

2. Written (signed and dated) informed consent.

3. Confirmed diagnosis by CT scan or MRI, of advanced epithelial ovarian, fallopiantube cancer, or primary peritoneal cancer with histologically- high-grade serous orendometrioid features or a predominantly serous/endometrioid component.

4. Tumour tissue expressing FRα (1+, 2+ or 3+ membrane staining on at least 5% oftumour cells by immunohistochemistry using the BN3.2 antibody (Leica Biosystems). i. Patients must be willing to provide an archival tumour tissue block or slides, orundergo procedure to obtain a new biopsy using a low risk, medically routineprocedure for immunohistochemistry (IHC) confirmation of FRα positivity ii. Note:Pre-screening for FRα expression may be performed at any point in advance of Cycle 1Day 1

5. Negative basophil activation test (BAT) prior to Cycle 1 Day 1. Note: this test maybe performed in duplicate at two different sites: (i) at the treatment centre (wherepossible), and (ii) at a reference laboratory. Where results are discordant, (or ininstances where the treatment centre is not able to perform the assay), thereference laboratory results will prevail.

6. Platinum-free interval since last line of platinum of less than 6 months (182 days).

7. Progressed following ≤4 prior regimens of anti-cancer therapy for ovarian cancer andno other authorised therapy is considered appropriate in the opinion of theinvestigator. Prior regimens can include carboplatin/paclitaxel, bevacizumab (ifclinically indicated), PARP inhibitors and FRα antibody-drug conjugates. i. Patients who received hyperthermic intraperitoneal chemotherapy (HIPEC) or otherIP therapies are eligible. ii. Neoadjuvant and adjuvant therapy counts as a prior regimen.

8. Has measurable disease as defined by RECIST v1.1 on CT or MRI scan with at least onelesion 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, afterdiscontinuation of the prior regimen. ii. Note: Lesions previously embolised, perfused, or irradiated without objectiveevidence of progression before Cycle 1 Day 1 are not allowed to be considered forresponse assessment.

9. No evidence of bowel obstruction.

10. ECOG Performance Status Score 0-1 prior to Cycle 1 Day 1.

11. Estimated life expectancy of >3 months, (91 days), in the opinion of theInvestigator.

12. 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 maynot be used to achieve this level. ii. Platelets ≥100 × 109/L (>100,000 per mm3) iii. Haemoglobin level >9 g/dLobtained within 14 days before Day 1. Packed red blood cell transfusion isacceptable, if the patient has a stable result of ≥9 g/dL for at least 1 weekpost-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) <1.5and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. Does not apply topatients 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)

13. Intact immune system as demonstrated by CD4 count ≥500 cells/mm3 and CD8 count ≥150cells/mm3.

14. Adequate renal function as demonstrated by creatine or measured and calculatedcreatinine clearance (estimated glomerular filtration rate [eGFR] can also be usedin place of creatinine or creatinine clearance [CrCl] - deduced using theCockcroft-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 patientwith creatinine levels >1.5 × institutional ULN.

15. Adequate hepatic function: i. Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for a patient withtotal bilirubin levels >1.5 × ULN. ii. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN or ≤5 × ULN for a patient with livermetastases. iii. Albumin ≥3.0 g/dL.

16. Recovered from all chemotherapy-related toxicities to Grade ≤1 according to CTCAEv5.0, excluding alopecia (any grade) and peripheral neuropathy (Grade ≤2).

17. No history of significant cardiac or pulmonary dysfunction, including but notlimited to interstitial pulmonary disease and chronic obstructive pulmonary disease.

18. No history of autoimmune disease.

19. Negative serum or urine pregnancy test.

20. Women of childbearing potential must have 2 negative pregnancy tests duringScreening, 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 aprevious hysterectomy or bilateral oophorectomy.

21. Female patients of child bearing potential must agree to practice true abstinence orto use two forms of contraception, one of which must be highly effective. Theseforms of contraception must be used from the time of signing consent, throughout thetreatment period, and for 6 months, (182 days), following the last dose of any studymedication. Oral or injectable contraceptive agents cannot be the sole method ofcontraception.

22. Willing and able to comply with all protocol-specified assessments and the trialvisit schedule.

23. Patient has been advised to take measures to avoid or minimise exposure of the skinto UV light, including sunbathing and solarium use for the duration of the trial andfor 4 weeks following last administration of MOv18 IgE.

Exclusion Criteria:

1. Non-epithelial tumour origin of the ovary, the fallopian tube, or the peritoneum (i.e., germ cell tumours).

2. Ongoing malignant ascites requiring drainage >500cc within 2 weeks prior to Day 1.

3. Anorexic and unable to eat.

4. Taking beta-blockers (at PI discretion) and unable to interrupt beta-blockade (whichmay counteract the therapeutic effects of adrenaline), or full dose tricyclicanti-depressants/MAOIs (which can dangerously augment the effects of adrenaline).These agents should be discontinued at least 4 half-lives before administration ofthe first dose of MOv18 IgE. Treatment may be reintroduced 48 hours post doseadministration. i. Note: Beta blockers may continue if, in the opinion of the Investigator, it wouldnot pose additional risk to the patient ii. Note: Only applies to full dosetricyclic anti-depressants. Low dose tricyclic anti-depressants to supportconditions such as peripheral neuropathy, chronic pain, or insomnia, may bepermitted at PI discretion

5. History of laryngeal oedema, uncontrolled or high-risk asthma, or anaphylaxis.Patients with a history of hypersensitivity to carboplatin, taxanes, or contrastmedia may enter the trial at the Investigator's discretion.

6. History of parasitic infections, such as helminthiasis.

7. Baseline elevation in serum tryptase (indicating possible mastocytosis) or apositive BAT. Tryptase normal range is 2-15 ng/mL.

8. Receiving systemic anti-cancer therapy, including immunostimulatory agents (e.g.,cytokine-based modality, antigen-specific peptide immunotherapy, immune checkpointblockade, co-stimulatory agonists) within 28 days of Cycle 1 Day 1.

9. Administration of other simultaneous chemotherapy drugs, anti-cancer therapy oranti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trialtreatment period (hormonal replacement therapy and denosumab is permitted).

10. Receiving radiation therapy within 14 days prior to Day 1. Local palliativeradiotherapy is permitted; however, if the radiotherapy is to a target lesion, thatlesion must be excluded from tumour response assessments.

11. Chronic treatment with systemic corticosteroids or other systemic immunosuppressivemedications (including but not limited to prednisone (>10 mg), cyclophosphamide,azathioprine, methotrexate, thalidomide, and anti-TNF agents) within 14 days priorto Day 1, or anticipated requirement for systemic immunosuppressive medicationsduring the trial.

12. Administration of a live, attenuated vaccine within 28 days prior to Day 1 oranticipation that such a live attenuated vaccine will be required during the trialor within 5 months, (152 days), after the last dose of MOv18 IgE. Influenzavaccination should be given during influenza season only. Patients must not receivelive, attenuated influenza vaccination. COVID vaccination is permitted asnecessitated.

13. Previous allogeneic bone marrow transplant or previous solid organ transplantation.

14. Historical positive serology test for human immunodeficiency virus (HIV).

15. History of autoimmune disease, including but not limited to inflammatory boweldisease, systemic lupus erythematosus, and autoimmune hepatitis.

16. History of interstitial lung disease or active pneumonitis.

17. Has a known hypersensitivity to a component of protocol therapy, MOv18 IgE or itsvehicle (sodium citrate, L-arginine, sucrose and polysorbate 20).

18. Positive serology for hepatitis B or C.

19. Uncontrolled concurrent illness including, but not limited to, ongoing or activeinfection, or psychiatric illness.

20. Has a history within last 12 months or ongoing clinically significant cardiovasculardisease such as unstable angina, myocardial infarction, or acute coronary syndrome,symptomatic or uncontrolled arrhythmia, left ventricular failure, congestive heartfailure, baseline ECG abnormalities that, in the Investigator's opinion, would belikely to interfere with their participation in the study, or with theinterpretation of the results, including, but not limited to, QTc prolongation togreater than 470 ms (as determined by the Fridericia formula), or any Class III orIV cardiac disease as defined by the New York Heart Association FunctionalClassification.

21. Concomitant use of drugs known to prolong QT/QTc interval (Appendix 1).

22. Has a fever ≥38oC within 3 days before the first dose of MOv18 IgE.

23. No other prior malignancy is allowed except for the following: adequately treatedbasal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treatedStage I or II cancer from which the patient is currently in complete remission (atleast to 5 years), or any other non-metastatic cancer controlled by surgery alone orsurgery plus radiotherapy from which the patient has been disease-free for 5 years.

24. Presence of CNS metastases (including spinal metastases) or CNS primary tumour,e.g., glioblastoma.

25. Clinically significant illness or major surgery within 4 weeks before theadministration of MOv18 IgE.

26. Currently breastfeeding.

27. Any condition which could interfere with, or the treatment for which might interferewith, the conduct of the trial, or which would, in the opinion of the Investigator,unacceptably increase the patient's risk by participating in the trial

28. Patient is under legal custodianship.

29. First-degree relatives of the Investigator, trial staff or Sponsor employees.