This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.
This Phase 1, open-label, first-in-human study will evaluate the safety, tolerability, immunogenicity, and pharmacokinetics profile of CTX-10726 monotherapy. Preliminary anti-tumor activity of CTX-10726 will also be assessed. The study will be conducted in 2 cohorts: Dose escalation and Dose expansion. The Dose Escalation Cohort will utilize a 3+3 design to evaluate four dose levels (0.3-10.0mg/kg) of CTX-10726 given as an IV infusion once every 2 weeks. Patients in the Dose Expansion Cohort will receive CTX-10726 as an IV infusion at dose(s) based on data from the Dose Escalation Cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Intravenous (IV) infusion (0.3-10.0mg/kg) every two weeks.
Nebraska Cancer Specialists
Omaha, Nebraska, United States
RECRUITINGSTART New York
Lake Success, New York, United States
RECRUITINGCohort 1: Evaluate the safety and tolerability of CTX-10726 by incidence of treatment-emergent adverse events (TEAEs) in escalating doses
Incidence of dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until 30 days after the last dose of CTX-10726, average of 6 months)
Cohort 1: Determine the dose(s) of CTX-10726 to be further examined in Cohort 2 and Phase 2 studies
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks ) until 30 days after the last dose of CTX-10726 (average of 6 months)
Cohort 2: Evaluate the safety and tolerability of CTX-10726 by incidence of treatment-emergent adverse events (TEAEs) at dose(s) selected from Cohort 1
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until 30 days after the last dose of CTX-10726 (up to 2 years)
Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Baseline until confirmed disease progression (up to 2 years)
Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: From the date of first confirmed complete response (CR) or partial response (PR) until the first date of recurrent or progressive disease (up to 2 years)
Disease Control Rate (DCR) percentage of patients with best overall response of CR, PR, or SD as per RECIST version 1.1
Time frame: From first dose of CTX-10726(Cycle 1 Day 1,Cycle = 2 weeks ) until disease progression or death, whichever occur first (up to 2 years)
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Clinical Benefit Rate (CBR) percentage of patients with best overall response of CR, PR, or SD for ≥ 6 months as per RECIST version 1.1
Time frame: From first dose of CTX-10726(Cycle 1 Day 1,Cycle = 2 weeks ) until disease progression or death, whichever occur first (up to 2 years)
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: From first dose of CTX-10726(Cycle 1 Day 1,Cycle = 2 weeks ) until disease progression or death, whichever occur first (up to 2 years)
Overall Survival (OS)
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1,Cycle = 2 weeks) until death (up to 2 years)
Maximum serum concentration (Cmax) of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1 = 2 weeks) until treatment discontinuation
Time of maximum serum concentration (Tmax) of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation
Trough concentration (Ctrough) of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation
Area under the curve (AUC) of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1,Cycle = 2 weeks) until treatment discontinuation
Clearance (CL) of serum concentrations of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation
Volume of distribution (Vd) of serum concentrations of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation
Terminal elimination half-life (t1/2) of serum concentrations of CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation
Dose response for CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation
Assess the immunogenicity of CTX-10726 screen for the presence and development of antibodies against CTX-10726
Time frame: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until end of treatment visit