Ensayos clínicos

Inclusion Criteria:

• Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
• Male or female ≥ 18 years old.
• Triple Negative Breast Cancer subjects only: Subject must have histologically or cytologically confirmed metastatic or locally recurrent ER-negative (< 1% by IHC), PR-negative (< 1% by IHC), and Her2-negative (either FISH negative, 0 or 1+ by IHC, or IHC2+ and FISH negative per ASCO/CAP definition) breast cancer. Subject must be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or intolerant of existing therapy(ies) known to provide clinical benefit or have no other available treatment options. Prior exposure to an immune checkpoint inhibitor is allowed. TP53MUT testing is not required.
• Serous Endometrial Cancer subjects only (Dose Exploration only): Subject must have histologically or cytologically confirmed diagnosis of metastatic or recurrent serous endometrial cancer, and be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic/recurrent setting or intolerant of existing therapy(ies) known to provide clinical benefit for their condition. TP53MUT testing is not required.
• Subjects with advanced or metastatic solid tumor with TP53MUT (Dose Exploration only, as assessed by local testing) that is unresectable and relapsed/refractory to at least one line of systemic chemotherapy or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
• Subjects must provide archived tumor samples (fresh frozen sample or formalin fixed, paraffin embedded [FFPE] sample collected within 5 years) or willing to undergo predosing tumor biopsy.
• Subjects willing to undergo pre/post-dose tumor biopsies. Subjects can be allowed to enroll without undergoing biopsy upon agreement with Investigator and the Medical Monitor if biopsy is not feasible.
• At least 1 measurable lesion ≥ 10 mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.
• Ability to take oral medications and willing to record daily adherence to Investigational product.
• Baseline QTc ≤ 470 msec for females and ≤ 450 msec for men.
• Adequate hematological laboratory assessments, as follows:
  • Absolute neutrophil count (ANC) ≥  1.5 x 10^9 /L without growth factor support within 7 days (G-CSF) or 14 days (pegylated G-CSF) from screening assessment;
  • Platelet count ≥ 100 x 10^9 /L without platelet transfusion within 7 days from screening assessment;
  • Hemoglobin > 9 g/dL (90 g/L) without red blood cell (RBC) transfusion within 7 days from screening assessment.
• Adequate renal laboratory assessments, as follows:
  • Calculated or measured creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation or 24 hour urine collection with plasma or urine creatinine concentrations, respectively.
• Adequate hepatic laboratory assessments, as follows:
  • AST < 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN);
  • ALT < 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN);
  • Total bilirubin < 1.5 x ULN (< 2.0 x ULN for subjects with liver metastases, documented Gilbert’s syndrome).
• Adequate coagulation laboratory assessments, as follows:
  • Prothrombin time (PT) or activated partial thromboplastin time (APTT) < 1.5 x upper limit of normal (ULN), OR International normalized ratio (INR) < 1.5 or within target range if on prophylactic anticoagulation therapy.
• Cardiac function, as follows:
  • Left ventricular ejection fraction (LVEF) > 50%

Eligibility last updated 4/18/22. Questions regarding updates should be directed to the study team contact.