A Study of ARGX-110 in Participants With Advanced Malignancies

A Phase I/II Study of ARGX-110 in Patients With Advanced Malignancies Expressing CD70.

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).

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: ARGX-110

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.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium
  • Edegem, Belgium
  • Gent, Belgium
• France
  • Bordeaux, France
  • Lille, France
  • Paris, France
  • Pierre-Bénite, France
  • Villejuif, France

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: Cohort 1; Participants will receive ARGX-110 as an intravenous infusion (IV) at dose level 1.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Dose Escalation: Cohort 2; Participants will receive ARGX-110 as an IV infusion at dose level 2.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Dose Escalation: Cohort 3; Participants will receive ARGX-110 as an IV infusion at dose level 3.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Dose Escalation: Cohort 4; Participants will receive ARGX-110 as an IV infusion at dose level 4.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Dose Escalation: Cohort 5; 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.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Safety Expansion: Cohort 1; 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.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Safety Expansion: Cohort 2; 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.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Safety Expansion: Cohort 3; 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.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Safety Expansion: Cohort 4; 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.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.
Experimental: Exploratory Efficacy: Cohort 5; Participants with relapsed/refractory CTCL will receive ARGX-110 as an IV infusion followed by a maintenance therapy at dose level 3.	Drug: ARGX-110; ARGX-110 will be administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose Limiting Toxicity (DLT)	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.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of ARGX-110	Plasma concentration of ARGX-110 will be assessed.	Up to 2 years
Biomarkers (CD70 qPCR and sCD27) of ARGX-110 biological activity	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.	Up to 2 years
Number of Participants who Achieve a Tumor Response	Tumor response will be assessed according to RECIST.	Up to 2 years

Collaborators and Investigators

• Sponsor: OncoVerity, Inc.
• Collaborators: Janssen Research & Development, LLC; argenx
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Silence K, Dreier T, Moshir M, Ulrichts P, Gabriels SM, Saunders M, Wajant H, Brouckaert P, Huyghe L, Van Hauwermeiren T, Thibault A, De Haard HJ. ARGX-110, a highly potent antibody targeting CD70, eliminates tumors via both enhanced ADCC and immune checkpoint blockade. MAbs. 2014 Mar-Apr;6(2):523-32. doi: 10.4161/mabs.27398. Epub 2013 Dec 6.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2013
• Primary Completion (Actual): July 10, 2020
• Study Completion (Actual): July 10, 2020

Study Registration Dates

• First Submitted: March 7, 2013
• First Submitted That Met QC Criteria: March 18, 2013
• First Posted (Estimated): March 19, 2013

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Malignancy
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CR108755; ARGX-110-1201 (Other Identifier: Janssen Research & Development, LLC); 2012-005046-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No