EPOCH: Eribulin and Pembrolizumab in Ovarian/​Uterine Carcinosarcoma (EPOCH)

• Drug: Eribulin Mesylate
• Drug: Pembrolizumab

Inclusion Criteria:

1. Provision of written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. prior to any study specific procedures and the ability to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.
2. Patients > 18 years old who have a histologically confirmed tubo-ovarian carcinosarcoma or uterine carcinosarcoma with evidence of recurrence or progression. The component of sarcomacancer arising from bones and/or soft tissue in the diagnostic pathologythe study of disease sample must be equal to or > 5% of tumoura tissue mass that forms from groups of unhealthy cells.
3. Must have Positron Emission Tomography (PET), Computerized Tomography CT, or Magnetic Resonance Imagingtests that create detailed images of areas inside the body (MRI) -proven relapsed disease after completion of at least one line and not more than two lines of chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
4. Must have at least one evaluable measurable lesion (other than the lesion that will be used for biopsyremoval of a section of tissue to analyse for cancer cells) using standard techniques according to the Response Evaluation Criteria in Solid Tumours (RECIST v1.1) guidelines (Appendix 1).
5. Have an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status of 0 to 1 (Appendix 5). Evaluation of ECOG is to be performed within 28 days prior to the first dosethe amount of medication taken of the study intervention.
6. Have adequate organ function as defined below (refer also Appendix 6).
   • Absolute neutrophil count (ANC) ≥1.5 x 109/L
   • Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding ≥100 x 109/L
   • Haemoglobin (Hb) ≥90 g/L or ≥5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red bloodthe red bodily fluid that transports oxygen and other nutrients around the body cell (pRBC) transfusion within last 2 weeks).
   • Creatinine ≤ 1.5 x Upper Limit Normal (ULN); OR Creatinine Clearance (CrCl) ≥ 30 mL/min (calculated per institutional standard) for participants with creatinine levels >1.5 ULN (glomerular filtration rate, GFR, can also be used in place of creatinine or CrCl). (Patients with moderate renal impairment (CrCl 30-49ml/min) will receive a 25% reduced dose of eribulin).
   • Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
   • Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
   • International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulantmedication used to prevent or reduce blood clots; also known as blood thinners therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants Biological specimens must be collected within 28 days prior to the first dose of the study intervention (within 7 days, where indicated in the SoA).
7. Available formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs and/or metastatic tumour from the up-front or secondary debulkingremoval of as much of the tumour as possible when complete tumour removal is not possible, also known as cytoreduction surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence with adequate neoplastic cell content (>30%).
8. Must have disease amenable to biopsy and must be willing to undergo a paired biopsy for additional correlative analyses (the first biopsy to be performed within 28 days prior to the start of the study intervention and the second biopsy in the five-day window prior to Cycle 2 (post Cycle 1)). For patients that experience progression of their disease whilst on study, separate patient consent will be sought for additional biopsies of their tumour for research.
9. Willing to have blood samples collected for translational research
10. Must not be pregnant, not breastfeeding, and at least one of the following conditions applies:
    1. Not a person of childbearing potential (POCBP). OR
    2. A POCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 months (120 days) after the last dose of the study treatment.