TLD-1, a Novel Liposomal Doxorubicin, in Patients With Advanced Solid Tumors

Key inclusion criteria for dose escalation part:

• Final protocol until amendment 2: Patients with either histologically or cytologically confirmed advanced or recurrent solid tumor who failed standard therapy or for whom no effective standard therapy is available

• From Amendment 3 on: Patients with histologically or cytologically confirmed advanced malignant tumors of the breast, ovary, uterine or sarcoma who failed standard therapy or for whom no effective standard therapy is available.

• Patients may have received up to 3 prior lines of palliative systemic chemotherapy

• Patients with brain metastases must have undergone definitive treatment (surgery and/or radiation) at least 1 month prior to starting study drug and be documented as having stable disease by imaging and are on stable doses of steroids for at least 2 weeks.

• Adequate bone marrow, renal and hepatic function

Key inclusion criteria for comparative PK part:

• Patients with either histologically or cytologically confirmed advanced or recurrent breast or ovarian cancer of all histologies

• Histologically-confirmed ovarian, fallopian tube or primary peritoneal cancer (collectively referred to herein as 'ovarian cancer') that is either platinum-resistant (disease progression within 6 months of the last receipt of platinum-based chemotherapy) or refractory (lack of response or disease progression while receiving the most recent platinum-based therapy).

• Patients with ovarian cancer may have received up to 3 lines of prior cytotoxic chemotherapy, but maximum 1 of them in the platinumresistant/ refractory setting. Confirmed high-grade serous, endometrioid, or carcinosarcoma histotypes are permitted.

• Patients with advanced or recurrent breast cancer may have received up to 2 prior lines of palliative cytotoxic chemotherapy.

• Patients with brain metastases must have undergone definitive treatment (surgery and/or radiation) at least 1 month prior to starting study drug and be documented as having stable disease by imaging and be on stable doses of steroids for at least 2 weeks.

• Adequate bone marrow, renal and hepatic function

Key exclusion criteria for dose escalation and comparative PK part:

• Significant cardiac disease or abnormality

• Patients who have received prior anthracyclines at a cumulative dose that exceeds 250mg/m2 for non-liposomal doxorubicin, 300mg/m2 for liposomal doxorubicin or 400mg/m2 for epirubicin and/or are refractory (during 3 months) to anthracyclines or have experienced allergic reactions or severe toxicity (grade 3 or 4) under anthracyclines

• Prior systemic chemotherapy/treatment for adjuvant/metastatic disease, radiotherapy, immunotherapy, or investigational agents within 28 days 5 half- life periods of previous therapy before registration.