A Phase I/II Study of TTI-621 in Combination with Doxorubicin in Patients with Unresectable or Metastatic High-Grade Leiomyosarcoma

Key Inclusion Criteria:

1. Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 0 or 1.

2. Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally advanced and not amenable to curative treatment with surgery or radiation.

   1. In the Dose Escalation phase, indications will be limited to high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma
   2. In the Dose Expansion phase, indications will be limited to high-grade leiomyosarcoma.
3. Objective evidence of disease progression unless disease is newly-diagnosed.
4. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (expansion cohorts).
5. Adequate organ and hematologic function.
6. No more than 1 prior treatment regimen for advanced disease, which is limited to gemcitabine with docetaxel.
7. Anthracycline-naïve.
8. Patients who were treated with a prior chemotherapy regimen must have completed treatment at least three weeks before initiation of study treatment.
9. All adverse events from prior treatment must be NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v5 Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.
10. Radiotherapy, including palliative radiotherapy, completed at least two weeks prior to treatment; palliative radiation to non-target lesions while on study is allowed.

Key Exclusion Criteria:

1. History of acute coronary syndromes.
2. History of or current Class II, III, or IV heart failure.
3. History or evidence of known CNS (central nervous system) metastases or carcinomatous meningitis.
4. Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) tract.
5. History of severe hypersensitivity reactions to antibodies.
6. Systemic steroid therapy.
7. History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
8. Prior organ transplantation including allogenic or autologous stem cell transplantation
9. Prior treatment with anti-CD47 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.