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

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