Refractory Tumor, Relapsed Solid Neoplasm, Solid Tumor
Conditions
Keywords
solid tumor
Brief summary
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
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.
Interventions
BIOLOGICALSTI-6643
Anti-CD47 human monoclonal antibody
Sponsors
Sorrento Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of STI-6643 | Baseline through study completion at up to approximately 31 months | Safety as assessed by incidence of adverse events, SAEs, DLTs, and clinically significant changes in safety lab results |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | Day 1 through study completion at up to approximately 31 months | Overall response rate |
| Duration of response | Day 1 through study completion at up to approximately 31 months | Duration of response |
| STI-6643 receptor occupancy | Day 1 through Day 22 | STI-6643 receptor occupancy |
| Anti-drug antibodies directed to STI-6643 | Day 1 through Day 15 | Anti-drug antibodies directed to STI-6643 |
| PK parameters | Day 1 through Day 22 | Evaluate the pharmacokinetics of STI-6643 |
Countries
United States
Contacts
Primary ContactMike Royal, MD
Outcome results
None listed