Two drugs called Idetrexed and olaparib are being evaluated. Idetrexed is a type of drug called an "aFR-targeted thymidylate synthase inhibitor". Idetrexed has been designed to selectively target cancer cells that have a protein called folate receptor on the surface of cancer cells. Thymidylate synthase is key to cancer cells for creating new DNA when they multiply. Blocking the action of thymidylate synthase with a drug like Idetrexed may therefore stop cancers from growing by damaging DNA in cancer cells. Olaparib is a type of drug called a "PARP inhibitor". It prevents cells repairing DNA damage. This leads to cells dying. Combining Idetrexed and olaparib should increase the number of cancer cells dying, especially those cells that have a lot of folate receptors. Cancer cells with a high number of folate receptors should be targeted more than normal healthy cells.

Inclusion Criteria:

• Histologically or cytologically proven high grade serous ovarian cancer refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient.
• Measurable (as defined by RECIST v1.1) or evaluable (based on tumour markers) disease.
• Life expectancy of at least 12 weeks.
• World Health Organisation (WHO) performance status of 0-1 (Appendix 1 of Protocol).
• Haematological and biochemical indices within the ranges shown in Protocol section 4.1.1). These measurements must be performed within one week (Day -7 to Day 1) prior to the patient's first dose of IMP.

Normal (no clinically significant abnormalities) 12-lead ECG, QTcF interval <470 ms

• Pulmonary function test FVC of >70%, DLCOc (DLCO corrected for Hb) of >60%.
• 18 years or over.
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
• For dose expansion patients only, they must have medium to high α-folate receptor expression according to the Ventana FOLR1-2.1 IHC assay.

Exclusion Criteria:

• Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.
• Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the DDU should not exclude the patient.
• Patients with new brain metastases. Patients with treated (surgically excised or irradiated) and stable brain metastases are eligible as long as the treatment was at least 4 weeks prior to initiation of study drug and brain MRI within 2 weeks of initiation of study drug is negative for new metastases.
• Patients with pulmonary metastases.
• History of thoracic radiation or other history likely to create pre-existing lung disease
• Presence of significant clinical ascites and/or pleural effusions.
• Female patients of child-bearing potential (or are already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one effective form plus a barrier method) [oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom] or agree to sexual abstinence (see Protocol Section 16.5 - Appendix 5), effective from signing the consent form, throughout the trial and for six months afterwards are considered eligible.
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• Patients with sub-acute bowel obstruction.
• Organ transplant patients.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• Patients with history of QT prolongation, clinically significant VT, VF, heart block, MI within 1 year, CHF NYHA Class III or IV, unstable angina, angina within 6 months, or other evidence of clinically significant coronary artery disease/
• Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I/Ib study of Idetrexed and Olaparib. Participation in an observational trial would be acceptable.
• Inability to tolerate Olaparib.
• Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
• Confirmed, current COVID-19 infection.

Cisgender women