Study of Anti-HB-EGF Antibody KHK2866 in Subjects With Advanced Solid Tumors and 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.