Evaluation of 64Cu-DOTA-U3-1287 in Subjects With Advanced Solid Tumors

Inclusion Criteria:

- Patient must have measurable disease as defined by RECIST 1.1, with the additional
requirement of at least one lesion ≥ 1.5 cm on CT scan or detectable on FDG-PET
performed within 30 days prior to screening

- Patient must have a tumor where HER3 expression is expected (this includes breast,
colon, lung, prostate, ovarian, cervical, endometrial, gastric, pancreatic, bladder,
head and neck, liver, and esophageal cancer, but other tumors will be considered
based on emerging HER3 expression data)

- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Patient must have pathologically documented, definitively diagnosed, advanced solid
tumors that are refractory to standard treatment or for which no curative therapy is
available

- Patient must have adequate hematologic and organ function as follows:

- Absolute neutrophils count (ANC) ≥ 1.5 x 109/L

- Platelet count ≥ 100 x 109/L

- Hemoglobin ≥ 9 g/dL

- Serum creatinine ≤ 2 x IULN

- AST ≤ 2.5 x IULN (≤ 5.0 x IULN if attributable to liver metastasis)

- ALT ≤ 2.5 x IULN (≤ 5.0 x IULN if attributable to liver metastasis)

- Alkaline phosphatase ≤ 2.0 x ULN (if bone or liver metastases are present, < 5 x
ULN)

- Total bilirubin ≤ 1.5 IULN

- Amylase or lipase ≤ 2.0 x IULN

- Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.5 x IULN

- Patient must have an LVEF of ≥ 50%

- Patient must be ≥ 18 years old

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry, for
the duration of study participation, and for 6 months following the completion of
study treatment; should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately.

- Patient must be willing and able to undergo the imaging studies outlined in the
protocol (in the opinion of the investigator)

- Patient must be able to understand and willing to sign an institutional review board
(IRB) approved informed consent form

- Patient must have archival tissue available for HER3 expression analysis

Exclusion Criteria:

- Patient must not have the liver and/or spleen as the only site(s) of disease (as
PET/CT imaging of 64Cu-DOTA-U3-1287 may be difficult in these anatomic locations)

- Patient must not have any unresolved toxicities > grade 1 with the exception of grade
2 lymphopenia and/or alopecia from prior anti-cancer therapy Note: Grade 2 or 3
toxicities from prior therapy that are considered irreversible (defined as having
been present and stable for > 3 months), such as ifosfamide-related proteinuria, or
treatment related neuropathy, may be allowed if they are not otherwise described in
the exclusion criteria AND the PI and Daiichi Sankyo both agree that this patient may
be included

- Patient must not have untreated or symptomatic primary central nervous system
metastases or symptoms of brain metastases; any stereotactic radiation or whole brain
radiation therapy must have been completed at least 4 weeks prior to study entry

- Patient must not have ascites or pleural effusion requiring medical intervention

- Patient must not have had a myocardial infarction within 6 months of Day 1 or any
unstable or uncontrolled disease/condition related to or impacting cardiac function
(i.e., unstable angina, congestive heart failure, New York Heart Association > class
II, uncontrolled hypertension [diastolic > 95 mmHg; systolic >140 mmHg])

- Patient not have cardiac arrhythmia or clinically significant ECG abnormalities

- Patient must not be known to be positive for human immunodeficiency virus (HIV)
infection, hepatitis C virus, or chronic active hepatitis B infection

- Patient must not have a known sensitivity to any components of the formulation

- Patient must not be receiving any concomitant antitumor treatment or chemotherapy,
radiotherapy, and hormonal therapy (with the exception of Lupron for prostate cancer
and SERMS for breast cancer subjects) within 4 weeks of Day 1 (6 weeks for
nitrosoureas or mitomycin and 2 weeks for small molecule tyrosine kinase inhibitors)

- Patient must not be receiving any concomitant immunosuppressant therapy (cyclosporine
A, FK506, etc., or chronic > 5 mg/d of prednisone)

- Patient must not be receiving any other concomitant investigational procedures and
must not have participated in any other clinical trial with an investigational device
or agent within 4 weeks of the first dose of 64Cu-DOTA-U3-1287

- Patient must not have had any previous exposure to U3-1287

- Patient must not have had any previous treatment with HER3 antagonists

- Patient must not have had G-CSF support therapy within 2 weeks of Day 1

- Patient must not have received red blood cell (RBC) transfusion within 2 weeks of Day
1

- Patient must not have received platelet transfusion within 2 weeks of Day 1

- Patient must not be pregnant or planning to become pregnant within 6 months after the
end of treatment; patient must not be breastfeeding

- Patient must not have a known sensitivity to any of the products to be administered
during dosing, including excipients, radiolabeled agents

- Patient must not have had major surgery within 28 days of Day 1 or predicted need for
major surgery while on study

- Patient must not schedule any elective surgeries (with the exception of port
placement or replacement) during his/her participation in the study and through 28
days after the last administration of U3-1287

- Patient must not have any comorbid medical disorder that may increase the risk of
toxicity in the opinion of the investigator or sponsor

- Inclusion of Women and Minorities

Both men and women and members of all races and ethnic groups are eligible for this trial.