Phase 1/2a Study of SQ3370 in Patients With Advanced Solid Tumors

A Multicenter Phase 1/2a, Open-Label Study of SQ3370 in Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of SQ3370 in patients with advanced solid tumors.

Phase 1: Inclusion Criteria:

1. Diagnosis of advanced soft tissue sarcoma or other solid tumors
2. Adequate hematologic, hepatic, renal, and coagulation function
3. ECOG performance status score 0-1
4. Tumor is the type where published clinical data would suggest that anthracyclines have cytotoxic activity
5. Injectable tumor present

Phase 1: Exclusion Criteria:

1. Prior exposure to 300 mg/m^2 of Dox HCl or DOXIL / CAELYX ® or 600 mg/m^2 of Epirubicin HCl

2. Congestive heart failure (CHF), severe myocardial insufficiency, or cardiac arrhythmia

3. Any of the following within 28 days prior to Cycle 1 Day 1:

   • Major surgery, as defined by the Investigator
   • Radiotherapy
   • Chemotherapy, immunotherapy and/or anticancer therapy (except for small molecule kinase inhibitors, which are 6 elimination half-lives)

4. Trastuzumab or trastuzumab emtansine dosed within 7 months prior to Cycle 1 Day 1.

5. Any transfusion within 14 days prior to Cycle 1 Day 1.

6. Pregnant or breast-feeding women.

7. Known active CNS metastases and/or carcinomatous meningitis or symptomatic brain metastasis. Participants with previously treated brain metastases may participate provided they are radiologically stable

8. History of allergic reactions attributed to Dox or other anthracyclines, NaHA, hyaluronic acid, or gram-positive bacterial proteins

9. History or evidence of clinically unstable/uncontrolled disorder, condition, or disease

Phase 2a Expansion Group 1 (Extremity STS): Inclusion

1. Patients with unresectable soft tissue sarcomas of the extremity AJCC Stage III OR select IV (=>5 cm injectable tumors) locally advanced and or metastatic, not amendable to primary surgical intervention according to the consensus of a multidisciplinary treatment team, determined prior to screening.
2. High grade STS, Grade 2/3, with an assessable/injectable lesion of at least diameter ≥5 cm by RECIST 1.1 criteria
3. No prior chemotherapy for STS, or radiation to affected limb

Phase 2a Expansion Group 1 (Extremity STS): Exclusion

1. Uncontrolled pain related to tumor
2. Open wounds or tissue necrosis related to tumor mass
3. Compartment syndrome or impending compartment syndrome

Phase 2a Expansion Group 2 (Unresectable STS): Inclusion

1. Locally advanced or metastatic, unresectable, soft-tissue sarcoma of intermediate or high grade with measurable disease.
2. Life expectancy >12 weeks (about 3 month)

Phase 2a Expansion Group 2 (Unresectable STS): Exclusion

1. Prior exposure to anthracyclines
2. Treatment naive extremity tumors

Phase 2a Expansion Group 3a (Head and Neck): Inclusion

1. Patients with histologically or cytologically confirmed squamous-cell carcinoma of the head and neck (HNSCC) who meet any of the following a) confirmed relapsed HNSCC or b) metastatic at initial presentation HNSCC
2. Patients who may have received two or less systemic regimens (therapies include chemotherapy and/or immunotherapy)

Phase 2a Expansion Group 3a (Head and Neck): Exclusion

1. Airway obstruction by tumor mass that requires clinical intervention
2. Prior treatment with anthracyclines