This is a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.
All patients must sign an informed consent in accordance with local institutional guidelines.
All patient must not have received prior PARPi including talazoparib
All patients must not have prior therapy with selinexor.
Age ≥ 18
Measurable disease by RECIST 1.1 criteria.
Eastern cooperative Oncology Group (ECOG) Performance Status of 0-1
Adequate bone marrow function and organ function within 2 weeks of study treatment
Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
Sequential
Talazoparib
DrugPatients will be treated with Talazoparib daily on a 4 weekly cycle (28 days)
Selinexor
DrugPatients will be treated with Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days)
safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0.
Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final Safety evaluations will be performed for all patients prior to each cycle of treatment, and include taking a medical history, physical examination, adverse event documentation, full blood count, renal function, liver function tests and electrocardiogram (ECG). Toxicities will be graded using the NCI CTCAE toxicity grading version 5.0.
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