Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)

Exclusion Criteria

• •8. Measurable disease by RECIST 1.1 criteria.
• •9. Eastern cooperative Oncology Group (ECOG) Performance Status of 0-1
• •10. Adequate bone marrow function and organ function within 2 weeks of study treatment
• •1. Adequate hematologic function defined as:
• •* Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
• •* Platelets ≥ 125 x 109/L during dose escalation phase; platelets ≥ 100 x 109/L during dose expansion phase
• •* Hemoglobin ≥ 9 x 109/L
• •2. Hepatic function:
• •* Bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• •* ALT or AST ≤ 2.5 times ULN (or ≤ 5 times ULN with liver metastases)
• •3. Adequate renal function:
• •* Calculated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/(72 x creatinine mg/dL); multiply by 0.85 if female.
• •11. Able to swallow tablets/ pills.
• •12. Able to comply with study-related procedures.
• •13. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for 7 months following the last dose of study treatment
• •1. Treatment within the last 30 days with any investigational drug.
• •2. Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
• •3. Major surgery within 28 days of study drug administration
• •4. Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• •5. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• •6. Pregnancy
• •7. Breast feeding
• •8. Poorly controlled diabetes mellitus
• •9. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment (for phase II only).
• •10. Symptomatic brain metastasis.
• •11. History of significant neurological or mental disorder, including seizures or dementia.
• •12. Unable to comply with study procedures
• •13. Current or anticipated use of strong P-gp inhibitors: amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, verapamil
• •14. Current or anticipated use of strong BCRP inhibitors: curcumin, cyclosporine A, eltrombopag, elacridar, fumitremorgin C, novobiocin, sulfasalazine