Phase 1 Study of Anti-HB-EGF Monoclonal Antibody KHK2866 as Monotherapy in Subjects With Advanced Solid Tumors and in Combination With Chemotherapy in Ovarian Cancer

Inclusion Criteria:

- Histologically or cytologically documented, measurable or non-measurable, advanced
primary or recurrent solid tumor (Phase 1a only) which is unresponsive to standard
therapy or for which there is no standard therapy available.

- Histologically or cytologically documented ovarian, primary peritoneal, or fallopian
tube cancer.

- The subject has objective radiographic disease progression and either unmeasurable or
measurable disease during or following the last treatment regimen, or serum cancer
antigen-125 (CA-125) greater than 2X the upper limit of normal ([ULN] >70 U/mL

- Life expectancy >3 months.

- Performance status < 3 at study entry.

- Age > 18 years.

- Normal left ventricular ejection fraction.

- Recovered from the effects of recent surgery, radiotherapy, chemotherapy, hormonal
therapy, or other therapies for cancer

- Preserved hepatic, renal, and hematopoetic organ function.

- Male and female subjects must use medically accepted contraception.

Exclusion Criteria:

- Ovarian malignancy of low malignant potential.

- Received anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or
investigational agents within 4 weeks prior to the first dose of KHK2866 (6 weeks for
nitrosourea or mitomycin chemotherapy).

- received Mabs or had major surgery within 4 weeks of the first dose of KHK2866.

- Requires administration of a prohibited medication or treatment including:
prophylactic use of erythroid and/or granulocyte colony stimulating factors;
concurrent anti-cancer treatment; biologic response modifiers for any condition

- Brain metastases, leptomeningeal or primary brain neoplasm, even if treated.

- Previously untreated or uncontrolled epidural metastasis

- Cerebrovascular accident, Transient ischemic attack; symptomatic head trauma, or
seizures or any kind within 6 months

- Dementia, or other disorders of mentation or difficulty speaking or difficulty with
comprehension.

- Suspected impending bowel obstruction

- The subject is pregnant,or is lactating.

- Significant uncontrolled intercurrent illness

- Known HIV infection or AIDS-related illness.

- Known active hepatitis B or C or other active liver disease.

- Psychiatric illness, disability or social situation that would compromise the
subject's safety, ability to provide consent, or limit his/her compliance with study
requirements.

- Experienced a unmanageable hypersensitivity reactions to Mabs or other therapeutic
proteins.

- History of second primary cancer, with the exception of: a) curatively resected
non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c)
other primary solid tumor treated with curative intent and no known active disease
present and no treatment administered during the last 2 years.

- Additional exclusion criteria for subjects proposed for enrollment into the Phase 1b
portion:

- History of hypersensitivity or infusion reaction to any of the proposed
chemotherapy arm's agents that could not be controlled with pre-medication
and/or infusion rate adjustment;

- Prior treatment with KHK2866;

- History of Grade ≥ 3 non-hematologic or Grade 4 hematologic toxicity
attributable to any of the proposed chemotherapy arm's agents

- For subjects proposed to receive treatment with KHK2866 plus PLD: prior total
cumulative exposure to doxorubicin must be ≤ 240 mg/m2.

- Subjects with a known history of interstitial lung disease or pulmonary fibrosis.
Subjects must have pulse oximetry >88% on room air at rest, and a DLco of >49% if
there is no evidence of lung metastasis.