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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Refractory Tumor; Relapsed Solid Neoplasm
• Intervention / Treatment: Biological: STI-6643

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mike Royal, MD; Phone Number: 4146 (858) 203-4100; Email: mroyal@sorrentotherapeutics.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • Not yet recruiting
      • University of California, San Diego
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Recruiting
      • Sanford Health
      • Contact: Staci Vogel; Phone Number: 605-328-1368; Email: staci.vogel@sanfordhealth.org
  • Texas
    • Austin, Texas, United States, 78758
      • Completed
      • NEXT Oncology - Austin
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Cancer Research
      • Principal Investigator: Reva Schneider, MD
      • Contact: Timothy Eamma; Phone Number: 214-658-1947; Email: TEamma@marycrowley.org
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
      • Contact: Carrie Friedman, RN; Email: Carrie.Friedman@usoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STI-6643; 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; Anti-CD47 human monoclonal antibody

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sorrento Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: solid tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 47MAB-ADVCA-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No