MC# 21-34 - A Phase I, 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

  • Agent(s): STI-6643
  • Disease Type(s): Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Monoclonal Antibody, Targeted Therapy
  • Molecular Target(s): CD47
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Mechanism of Action

STl-6643 targets and binds to CD47 expressed on tumor cells, blocking the interaction of CD47 with signal regulatory protein alpha (SIRPa) expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of macrophage activation and phagocytosis of cancer cells. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1 ), which is expressed on macrophages, and results in macrophage activation and the specific phagocytosis of tumor cells.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of STI-6643 can be given with an acceptable level of side effects
  • The effects of STI-6643 (good and bad)
  • How much of STI-6643 is absorbed into the blood and how fast it is removed
Inclusion Criteria
  1. Signed informed consent
  2. Age ≥ 18 years
  3. ECOG Performance Status ≤ 2
  4. Histologically- or cytologically-confirmed solid tumor
  5. Patient has relapsed, is refractory to, or intolerant of standard of care therapy
  6. No available approved therapy that may provide clinical benefit (per Investigator)
  7. Measurable or evaluable disease by RECISTv1.1
  8. Life expectancy of > 12 weeks (per Investigator)
  9. Adequate laboratory parameters including:
    • Absolute neutrophil count (ANC) ≥ 1500/mm3
    • Platelets ≥ 100,000/mm3
    • Hemoglobin ≥ 12 g/dL (in the absence of transfusion over the prior 2 weeks)
    • AST/SGOT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
    • ALT/SGPT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
    • Total bilirubin ≤ 2.0 x ULN (unless diagnosis of Gilbert’s syndrome in which case < 3.0 times ULN)
    • Serum creatinine ≤ 2.0 x ULN or estimated GFR ≥ 45 mL/min (per Cockcroft-Gault equation)
  10. If residual treatment related toxicity from prior therapy:
    • a. Treatment related toxicity resolved to ≤ Grade 1 (alopecia excepted), or
    • b. Treatment related toxicity resolved to ≤ Grade 2 with prior approval of the Medical Monitor
  11. Willingness to comply with the study schedule and all study requirements
  12. [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
  13. [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
  14. [Males] Willingness to refrain from donating sperm throughout the study and for at least 30 days following the last dose
  15. [Females] If of child-bearing potential, must have a negative serum pregnancy test
Exclusion Criteria
  1. Participating in any other interventional clinical study
  2. Previous exposure to an anti-CD47 or SIRPα antibody
  3. ≤ 28 days (or 5 half-lives if shorter) between of systemic anti-tumor treatment (eg, chemotherapy, endocrine therapy, immunotherapy, cellular therapy) and C1D1
  4. ≤ 28 days from prior irradiation (≤ 7 days from limited field irradiation for control of symptoms) and C1D1
  5. ≤ 28 days between major surgery (≤ 7 days from minor surgical procedures, no waiting period following central catheter placement)
  6. ≤ 7 days between administration of G-CSF, GM-CSF, erythropoietin, thrombopoietin or IL11 and C1D1
  7. ≤ 7 days between systemic immunosuppressive therapy in excess of 10 mg/day prednisone equivalent and C1D1 (topical or inhaled corticosteroids not restricted)
  8. ≤ 28 days between a live attenuated vaccine and C1D1
  9. Known central nervous system (CNS) involvement with tumor (eg, metastases, meningeal carcinomatosis)
  10. Active second malignancy requiring ongoing systemic treatment
  11. History of primary immunodeficiency disorders
  12. History of active pulmonary tuberculosis
  13. History of COVID-19 symptoms unless COVID-19 test negative ≤ 72 hours of C1D1
  14. ≤ 12 weeks from an allogeneic hematopoietic stem cell transplant and C1D1 or active graft-versus-host disease (GvHD)
  15. Active infection (eg, bacterial, viral, fungal) requiring systemic treatment ≤ 72 hours of C1D1
  16. Known HIV-positive with CD4+ cell counts < 350 cells/uL or a history of an AIDSdefining opportunistic infection
  17. Known T-cell leukemia virus type 1 (HTLV1) infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia
  18. Significant risk for HBV reactivation (defined as HBsAg positive, HBcAb positive or HBV DNA positive)
  19. Detectable HCV RNA
  20. Pregnant or breast feeding
  21. History of clinically significant cardiovascular abnormalities including:
    • a. Congestive heart failure (NYHA classification ≥ 3) within 6 months of C1D1
    • b. Unstable angina pectoris
    • c. ≤ 6 months from myocardial infarction and C1D1
    • d. Arrhythmias (other than atrial fibrillation) requiring ongoing treatment
    • e. QTcF interval > 480 msec (using Fridericia’s formula)
    • f. Uncontrolled hypertension (ie, systolic BP > 180 mmHg or diastolic BP > 100 mmHg)
  22. 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

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://www.clinicaltrials.gov/ct2/show/NCT04900519

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Re: MC# 21-34