A Phase I/II, Multi-Center, Open-Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR610 Given Weekly in Subjects With Solid Tumors

Inclusion Criteria:

- Signed informed consent

- Age 18 years or more

- Histologically-confirmed, progressive, locally advanced or metastatic solid tumor

- Failed, refused, or not eligible for standard of care therapy

- ECOG performance status of 0, 1, or 2

- At least 30 days from prior anticancer therapy including chemotherapy, hormonal
(except for the control of prostate cancer which may be continued),
investigational, biological and irradiation

- No remaining grade 1 or higher toxicity from prior cancer therapies

- At least four (4) weeks from prior major surgery

- Women of child-bearing potential must be willing to use an acceptable contraceptive
method and must have a negative urine or serum pregnancy test within 2 weeks prior to
beginning treatment on this trial

- Sexually active men must be willing to use an acceptable contraceptive method

- Adequate hematological and biological function

- Willingness to participate in PK sampling during cycles 1 and 2

- Willingness to provide permission to access archived tumor samples for evaluation of
EGFR mutation status

- Willingness to provide samples for storage of normal tissue containing wild-type DNA

Additional Inclusion Criteria during Expansion Phase

- Stage IIIB to IV, non-squamous, non-small cell lung cancer (NSCLC) with known
sensitizing mutations in EGFR, and the T790M resistance mutation

- At least one target lesion as defined by RECIST 1.1 that allows for evaluation of
tumor response

Exclusion Criteria:

- Pregnant or nursing women

- Any uncontrolled medical illness including, but not limited to, significant
gastrointestinal disorders, cardiovascular disease, or interstitial lung disease

- History of clinically significant cardiovascular abnormalities, eg., uncontrolled
hypertension, CHF (NYHA classification ≥2), unstable angina, poorly controlled
arrhythmias, myocardial infarction within 6 months of study entry, implantable
pacemaker or implantable cardioverter defibrillator

- Clinically significant abnormal 12-lead ECG with QTcF >450 msec

- Use of any medications known to produce QT prolongation

- Family history of Long QT Syndrome

- Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or
equivalent) ≥400 mg/m2

- Cardiac left ventricular function with resting ejection fraction of less than 50%

- Symptomatic CNS lesions or known CNS lesions that require therapy

- Prior therapy with an irreversible EGFR inhibitor

- Prior history of an allergic reaction to a tyrosine kinase inhibitor

Additional Exclusion Criteria during Expansion Phase

- Any other malignancy likely to effect the assessment of toxicity or efficacy of PR610