A Study of ARGX-110 in Participants With Advanced Malignancies

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: ARGX-110


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: Cohort 1<br>Participants will receive ARGX-110 as an intravenous infusion (IV) at dose level 1. | Drug: ARGX-110<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Dose Escalation: Cohort 2<br>Participants will receive ARGX-110 as an IV infusion at dose level 2. | Drug: ARGX-110<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Dose Escalation: Cohort 3<br>Participants will receive ARGX-110 as an IV infusion at dose level 3. | Drug: ARGX-110<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Dose Escalation: Cohort 4<br>Participants will receive ARGX-110 as an IV infusion at dose level 4. | Drug: ARGX-110<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Dose Escalation: Cohort 5<br>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<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Safety Expansion: Cohort 1<br>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<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Safety Expansion: Cohort 2<br>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<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Safety Expansion: Cohort 3<br>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<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Safety Expansion: Cohort 4<br>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<br>* ARGX-110 will be administered as an IV infusion.<br>|
| Experimental: Exploratory Efficacy: Cohort 5<br>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<br>* ARGX-110 will be administered as an IV infusion.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignancy