A Study in Cancer Patients to Evaluate the Effect of a Single Dose of NKTR-102 (Etirinotecan Pegol) on the QTc Interval and to Assess Pharmacokinetics and Safety

A Phase 1 Study to Evaluate the Effect of Nktr-102 for Injection (Etirinotecan Pegol) on the QT/QTC Interval in Patients With Advanced or Metastatic Solid Tumors

The purpose of this research study is to evaluate the effect of NKTR-102 on the QT/QTc interval in patients with advanced or metastatic solid tumors

This is an open-label study that will assess the effect of NKTR- 102 on cardiac ventricular repolarization, as characterized by QTcF (QT interval with Fridericia correction) interval values, in patients with advanced or metastatic solid tumors following administration of a single dose of NKTR-102.

Inclusion Criteria:

• Advanced or metastatic solid tumor refractory to standard therapy
• Measurable or non-measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Resolution of acute toxic effects of prior chemotherapy and other cancer treatments
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram
• Adequate bone morrow and organ function
• Electrolytes within normal limits
• Stopped tobacco use for 4 weeks prior to day 1 and during the study
• Agree to use adequate contraception

Exclusion Criteria:

• Previous anti-cancer therapy for malignancy within 4 weeks (6 weeks for the nitrosoureas or mitomycin C) before day 1
• Treatment with antiarrythmic drugs and any medication known to cause QTc prolongation within 4 weeks before screening and during the study
• Prior extensive anthracycline exposure
• Administration of cytochrome P450 CYP3A4 inducers and inhibitors within 4 weeks before day 1 and during the study
• Intake of grapefruit, grapefruit juice, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days prior to day 1 and during the study
• History of serious cardiovascular disease
• Abnormal systolic blood pressure, diastolic blood pressure and/or heart rate
• History of additional risk factors for Torsade de Pointes
• Prolonged QTcF
• Important abnormalities of the ECG that may interfere with the interpretation of QTc interval changes at screening
• Implantable pacemaker or automatic implantable cardioverter defibrillator
• UGT1A1 genotype of TA 7 in both alleles (homozygous UGT1A1*28) or TA 8 in either one or both alleles (hetero- or homozygous for UGT1A1*37)
• Any major surgery within 4 weeks prior to day 1
• Concurrent treatment with other anticancer therapy
• Untreated central nervous system metastases
• Chronic or acute GI disorders resulting in diarrhea
• Pregnancy or lactation