Study of the Safety and Efficacy of STI-6643 in Subjects With Advanced Solid Tumors

A Phase 1, Open-Label, Dose-Escalation Study of the Safety and Efficacy of STI-6643, an Anti-CD47 Human Monoclonal Antibody, in Subjects With Advanced Solid Tumors

This is a first-in-human, phase 1, open-label, dose-escalation study of STI-6643 administered by intravenous infusion in subjects with a relapsed/refractory advanced solid tumor.

This is a first-in-human, phase 1, open-label, dose-escalation study of STI-6643 administered by intravenous infusion in subjects with a relapsed/refractory advanced solid tumor.

The study will determine an MTD and RP2D using a conventional 3+3 study design with priming dose identification (PDI) stage and therapeutic dose (TD) escalation (TDE) stage. Dose limiting toxicity evaluated over the initial 28 days of STI-6643 administration.

Inclusion Criteria:

• Signed informed consent

• Age ≥ 18 years

• ECOG Performance Status ≤ 2

• Histologically- or cytologically-confirmed solid tumor

• Patient has relapsed, is refractory to, or intolerant of standard of care therapy

• No available approved therapy that may provide clinical benefit (per Investigator)

• Measurable or evaluable disease by RECISTv1.14

• Life expectancy of > 12 weeks (per Investigator)

• Adequate laboratory parameters including:

  1. Absolute neutrophil count (ANC) ≥ 1500/mm3
  2. Platelets ≥ 100,000/mm3
  3. Hemoglobin ≥ 12 g/dL (in the absence of transfusion over the prior 2 weeks)
  4. AST/SGOT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
  5. ALT/SGPT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
  6. Total bilirubin ≤ 2.0 x ULN (unless diagnosis of Gilbert's syndrome in which case < 3.0 times ULN)
  7. Serum creatinine ≤ 2.0 x ULN or estimated GFR ≥ 45 mL/min (per Cockcroft- Gault equation)

• If residual treatment related toxicity from prior therapy:

  1. Treatment related toxicity resolved to ≤ Grade 1 (alopecia excepted), or
  2. Treatment related toxicity resolved to ≤ Grade 2 with prior approval of the Medical Monitor

• Willingness to comply with the study schedule and all study requirements

• [Females] Must be postmenopausal, surgically sterile, or agree to use adequate contraception (per Investigator) throughout the study and for a least 30 days following the last dose

• [Males] Must be surgically sterile or must agree to use adequate contraception (per Investigator) throughout the study and for at least 30 days following the last dose

• [Males] Willingness to refrain from donating sperm throughout the study and for at least 30 days following the last dose

• [Females] If of child-bearing potential, must have a negative serum pregnancy test

Exclusion Criteria:

• Participating in any other interventional clinical study

• Previous exposure to an anti-CD47 or SIRPα antibody

• ≤ 28 days (or 5 half-lives if shorter) between of systemic anti-tumor treatment (e.g., chemotherapy, endocrine therapy, immunotherapy, cellular therapy) and the 1st dose of STI-6643

• ≤ 28 days from prior irradiation (≤ 7 days from limited field irradiation for control of symptoms) and the 1st dose of STI-6643

• ≤ 28 days between major surgery (≤ 7 days from minor surgical procedures, no waiting period following central catheter placement)

• ≤ 7 days between administration of G-CSF, GM-CSF, erythropoietin, thrombopoietin or IL11 and the 1st dose of STI-6643

• ≤ 7 days between systemic immunosuppressive therapy in excess of 10 mg/day prednisone equivalent and the 1st dose of STI-6643 (topical or inhaled corticosteroids not restricted)

• ≤ 28 days between a live attenuated vaccine and the 1st dose of STI-6643

• Known central nervous system (CNS) involvement with tumor (e.g., metastases, meningeal carcinomatosis)

• Active second malignancy requiring ongoing systemic treatment

• History of primary immunodeficiency disorders

• History of active pulmonary tuberculosis

• History of COVID-19 symptoms unless COVID-19 test negative ≤ 72 hours of the 1st dose of STI-6643

• ≤ 12 weeks from an allogeneic hematopoietic stem cell transplant and C1D1 or active graft-versus-host disease (GvHD)

• Active infection (e.g., bacterial, viral, fungal) requiring systemic treatment ≤ 72 hours of the 1st dose of STI-6643

• Known HIV-positive with CD4+ cell counts < 350 cells/uL or a history of an AIDS defining opportunistic infection

• Known T-cell leukemia virus type 1 (HTLV1) infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia

• Significant risk for HBV reactivation (defined as HbsAg positive, HbcAb positive or HBV DNA positive)

• Detectable HCV RNA

• Pregnant or breast feeding

• History of clinically significant cardiovascular abnormalities including:

  1. Congestive heart failure (NYHA classification ≥ 3) within 6 months of the 1st dose of STI-6643
  2. Unstable angina pectoris
  3. ≤ 6 months from myocardial infarction and the 1st dose of STI-6643
  4. Arrhythmias (other than atrial fibrillation) requiring ongoing treatment
  5. QTcF interval > 480 msec (using Fridericia's formula)
  6. Uncontrolled hypertension (i.e., systolic BP > 180 mmHg or diastolic BP > 100

• Any condition, including the presence of laboratory abnormalities, that places the subject at an unacceptable risk if the subject was to participate in the study.