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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Solid Tumor, Relapsed Solid Neoplasm, Refractory Tumor

Intervention / Treatment
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* Biological: STI-6643


Participation Criteria
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Eligibility Criteria
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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: 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) If residual treatment related toxicity from prior therapy: Treatment related toxicity resolved to ≤ Grade 1 (alopecia excepted), or 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: Congestive heart failure (NYHA classification ≥ 3) within 6 months of the 1st dose of STI-6643 Unstable angina pectoris ≤ 6 months from myocardial infarction and the 1st dose of STI-6643 Arrhythmias (other than atrial fibrillation) requiring ongoing treatment QTcF interval > 480 msec (using Fridericia's formula) 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STI-6643<br>STI-6643 will be provided in a single use 10-mL high borosilicate type 1 glass vial at a concentration of 500mg/10 mL (50 mg/mL) administered intravenously weekly for 4 weeks, then biweekly for Cycles 2 and up. | Biological: STI-6643<br>* Anti-CD47 human monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of STI-6643 | Safety as assessed by incidence of adverse events, SAEs, DLTs, and clinically significant changes in safety lab results | Baseline through study completion at up to approximately 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Overall response rate | Day 1 through study completion at up to approximately 31 months | 
| Duration of response | Duration of response | Day 1 through study completion at up to approximately 31 months | 
| STI-6643 receptor occupancy | STI-6643 receptor occupancy | Day 1 through Day 22 | 
| Anti-drug antibodies directed to STI-6643 | Anti-drug antibodies directed to STI-6643 | Day 1 through Day 15 | 
| PK parameters | Evaluate the pharmacokinetics of STI-6643 | Day 1 through Day 22 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumor