A Study of ARGX-110 in Participants With Advanced Malignancies
- Registration Number
- NCT01813539
- Lead Sponsor
- OncoVerity, Inc.
- Brief Summary
The purpose of this study is to determine the optimal dose of ARGX-110 in participants with advanced malignancies and to assess efficacy of ARGX-110 (exploratory efficacy cohort 5 only).
- Detailed Description
Phase I study conducted in participants whose tumors express the target of interest. Pharmacokinetics (PK), pharmacodynamics (PD), biomarkers will be determined to support dose selection.
Phase II study conducted in Cutaneous T-cell lymphoma (CTCL) participants who are CD70 positive. PK, PD, biomarkers and immunohistochemistry (IHC) will be determined to assess efficacy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 99
- Histological diagnosis of malignancy refractory to, or relapsing after standard therapy
- Solid tumors or T-cell malignancies positive for the CD70 antigen by Immunohistochemistry/Fluorescence-activated cell sorting (IHC/FACS) within 56 days prior to administering the first dose of ARGX-110. IHC criterion: greater than > 10 percent (%) of CD70 positive tumor cells
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or 2
- Serum albumin greater than or equal to (>=) 20 gram per liter (g/L) (solid tumor only)
- Ability to comply with protocol-specified procedures/evaluations and scheduled visits. In particular, the ability of the patient to undergo a tumor biopsy (optional for safety expansion cohort 4)
- History or clinical evidence of neoplastic central nervous system (CNS) involvement
- History of another primary malignancy that has not been in remission for at least 1 year
- Systemic glucocorticoid administration at doses greater than physiological replacement (prednisolone 20 milligram [mg] equivalent) within 28 days of ARGX-110 first dose administration (for T-cell malignancies higher systemic dose can be allowed following discussion with Sponsor)
- Major surgery within 28 days of ARGX-110 first dose administration
- Unresolved grade 3 or 4 toxicity from prior therapy, including experimental therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: Cohort 2 ARGX-110 Participants will receive ARGX-110 as an IV infusion at dose level 2. Safety Expansion: Cohort 2 ARGX-110 Participants with hematological malignancies (all etiologies) will receive ARGX-110 as an IV infusion at a dose based on the safety, PD, and PK profiles of ARGX-110 as per the dose escalation part of the trial. Dose Escalation: Cohort 3 ARGX-110 Participants will receive ARGX-110 as an IV infusion at dose level 3. Dose Escalation: Cohort 4 ARGX-110 Participants will receive ARGX-110 as an IV infusion at dose level 4. Safety Expansion: Cohort 1 ARGX-110 Participants with solid tumors will receive ARGX-110 as an IV infusion at a dose based on the safety, PD, and PK profiles of ARGX-110 as per the dose escalation part of the trial. Safety Expansion: Cohort 3 ARGX-110 Participants with cutaneous T-cell lymphoma (CTCL) will receive ARGX-110 as an IV infusion at dose level 2 followed by a maintenance therapy at dose level 2 or 3. Exploratory Efficacy: Cohort 5 ARGX-110 Participants with relapsed/refractory CTCL will receive ARGX-110 as an IV infusion followed by a maintenance therapy at dose level 3. Dose Escalation: Cohort 1 ARGX-110 Participants will receive ARGX-110 as an intravenous infusion (IV) at dose level 1. Safety Expansion: Cohort 4 ARGX-110 Participants with peripheral T-cell lymphoma (PTCL) will receive ARGX-110 as an IV infusion at dose level 2 followed by a maintenance therapy at dose level 2 or 3. Dose Escalation: Cohort 5 ARGX-110 Participants will receive ARGX-110 as an IV infusion at intermediate dose level at the conclusion of Cohort 4 prior to opening the safety expansion cohorts to participants enrolment.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose Limiting Toxicity (DLT) 21 days DLT is defined as drug-related grade 3 or 4 clinical adverse event (AE) occurring during the 21 days (3 weeks) following the first dose of ARGX-110.
- Secondary Outcome Measures
Name Time Method Biomarkers (CD70 qPCR and sCD27) of ARGX-110 biological activity Up to 2 years Biomarkers (CD70 quantitative polymerase chain reaction \[CD70 qPCR\] and soluble CD27 \[sCD27\]) will be measured in serum and on tumor samples to correlate systemic drug effects with AE and Tumor response.
Number of Participants who Achieve a Tumor Response Up to 2 years Tumor response will be assessed according to RECIST.
Plasma Concentrations of ARGX-110 Up to 2 years Plasma concentration of ARGX-110 will be assessed.