Breast Cancer Clinical Trials

∙ Patients must meet all of the following criteria:

• Female ≥18 years of age.

• Written (signed and dated) informed consent.

• Histologically or cytologically confirmed advanced, recurrent or metastatic ovarian cancer, endometrial cancer, triple-negative breast cancer i. Ovarian cancer: must have epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with high-grade serous or endometrioid features or a predominantly serous/endometrioid component ii. Endometrial cancer: must have advanced, recurrent or metastatic, endometrial cancer (any subtype excluding endometrial sarcoma) iii. Triple Negative Breast cancer: must have advanced, recurrent or metastatic triple-negative breast cancer (based on the most recently analyzed biopsy from locally recurrent or metastatic site, local laboratory) meeting the following criteria:

‣ HER2-negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+

⁃ ER and PgR expressions \<10% as determined locally by IHC assay as per most recent ASCO/CAP guidelines

• Tumour tissue expressing FRα on at least 5% of tumour cells, as determined by immunohistochemistry using either (i) the BN3.2 antibody (Leica Biosystems) or (ii) the FOLR1 (FOLR1-2.1) antibody (Ventana) Note: All patients must be willing to provide an archival tumour tissue block, or undergo a procedure to obtain a new biopsy, using a low risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity using BN3.2 antibody (Leica Biosystems).

• Note: Pre-screening for FRα positivity, using BN3.2 antibody (Leica Biosystems), may be performed at any point in advance of the first administration of MOv18 IgE i. Leica Biosystems BN3.2 antibody 1+ 2+ 3+ staining ii. Ventana FOLR1 antibody criteria 2+ 3+ membrane staining Note: Patients with a medical history confirming tumour tissue expression of FRα, as confirmed by the Ventana FOLR1 antibody, will be considered as meeting inclusion Criteria #4 and will not require a confirmation via Leica Biosystems assay prior to receiving MOv18 IgE. However, in all instances, confirmation of FRα expression using the BN3.2 antibody (Leica Biosystems), will be required to be tested during the trial. Confirmation is not required prior to C1D1.

• Note: Discordant results between the two systems will not result in patient removal from the trial unless deemed appropriate by the treating Investigator.

• Negative basophil activation test (BAT) prior to the first administration of MOv18 IgE.

• Note: this test will be performed at a reference laboratory.

• Ovarian cancer: platinum-free interval since last dose of platinum, of less than 6 months (182 days).

• Prior therapies:

• Ovarian cancer: progressed following ≤2 prior regimens of anti-cancer therapy for platinum resistant ovarian cancer, and, at the time, no other authorised therapy is considered appropriate by the treating investigator.

• i. Patients who received hyperthermic intraperitoneal chemotherapy (HIPEC) or other IP therapies are eligible.

• Endometrial cancer: progressed after any prior line of systemic therapy, and, at the time, no other authorised therapy is considered appropriate by the treating investigator.

• Breast cancer: progressed after any prior line of systemic therapy, and, at the time, no other authorised therapy is considered appropriate by the treating investigator.

• Has measurable disease as defined by RECIST v1.1 on CT or MRI scan i. Note: Baseline scans must be performed ≤28 days before the first administration of MOv18 IgE, after discontinuation of the prior regimen.

• ii. Note: Lesions previously embolised, perfused, or irradiated without objective evidence of progression before the first administration of MOv18 IgE are not allowed to be considered for response assessment.

• No evidence of bowel obstruction.

⁃ ECOG Performance Status Score 0-1 prior to the first administration of MOv18 IgE.

⁃ Estimated life expectancy of \>3 months, 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 the first administration of MOv18 IgE. 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 either estimated glomerular filtration rate \[eGFR\] or calculated creatinine clearance \>45 mL/min (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 active or history of autoimmune disease, (with exception of vitiligo, type I DM, residual hypothyroidism due to autoimmune condition only requiring hormone replacement) and/or no history of autoimmune disease that required treatment with steroids or immunosuppressive medication within 6 months of the first administration of MOv18 IgE.

⁃ 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. 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.