Paxalisib Plus Olaparib or Pembrolizumab/Chemotherapy in Advanced Breast Cancer

ACTRN 12624001340527

Brief Summary

This study aims to learn about the safety and tolerability of the study drug, paxalisib when taken by female participants with advancedat a late stage, far along breast cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.

Intervention/Treatment

• Drug: Paxalisib.
• Drug: Olaparib.
• Drug: Pembrolizumab.
• Drug: Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.

Inclusion Criteria

1. Participants must be female and at least 18 years of age inclusive, at the time of signing the 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..
2. Participants who are:
   • Arm A, Paxalisib plus Olaparib:
     1. HER2-negative stage IV (metastatic) breast cancer diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results based on pre-existing documented histopathology and medical imagingtests that create detailed images of areas inside the body results.
     2. Confirmed gBRCAm (BRCA1, BRCA2 or both).
     3. Prior treatment with chemotherapy in the metastatic setting.
   • Arm B, Paxalisib plus Pembrolizumab/chemotherapy:
     • 1. Recurrent, unresectable or metastatic triple-negative breast cancer diagnosis, based on preexisting documented histopathology and medical imaging results.
       2. Confirmed PD-L1 (CPS greater than or equal to 10) positive.
       3. Treatment in combination with chemotherapy.
       4. No prior PD-1/PD-L1 therapy.
3. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and with the applicable Consumer Medicines Information Sheet/s for the non-investigational medicinal products.
4. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
5. Life expectancy greater than 12 weeks.
6. At least one confirmed measurable lesion by RECIST 1.1 criteria (iRECIST for Arm B).
7. Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status 0 or 1.
8. Satisfies the following haematologic, renal and hepatic function tests:
   1. Haematologic tests:
      • Absolute neutrophil count greater than or equal to 1.5 x 10^9L
      • Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding greater than or equal to 100 x 10^9L
      • Haemoglobin greater than or equal to 90 g/L
   2. Bloodthe red bodily fluid that transports oxygen and other nutrients around the body coagulation tests:
      • Prothrombin time (PT) less than or equal to 1.5 x upper limit of normal (ULN).
      • Activated partial thromboplastin time (aPTT) less than or equal to 1.5 x ULN.
   3. Hepatic function tests:
      • Total bilirubin less than or equal to 1.5 x ULN.
      • AST and ALT less than or equal to 2.5 x ULN [less than or equal to 5 x ULN in case of liver metastases].
   4. Renal function tests:
      • Creatinine less than or equal to 1.5 x ULN OR creatinine clearance (CrCl) greater than or equal to 30 mL/min for a patient with creatine levels greater than 1.5 x ULN.
9. Willing and able to comply with the protocol as judged by the Investigator.
10. Patients must be willing to forego other drug therapy against the tumor while enrolled in the study.