A Study of ARGX-110 in Combination With Azacytidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)

NCT03030612 | Completed Phase 1 DMC

• 3 other identifiers: CR1087562016-002151-17ARGX-110-1601
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) of ARGX-110 and/or the recommended Phase II dose (RP2D) in combination with a standard dose of azacytidine (AZA) in Phase 1; and to evaluate efficacy of ARGX-110 when administered at a RP2D level established in Phase I in combination with a standard dose of AZA (proof-of concept) by evaluating overall response rate (ORR) in Phase 2.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Participants with Dose Limiting Toxicity (DLT)

  DLTs will be defined as any of the following drug-related events: Any grade 3 or higher drug related non-hematological toxicity or; Grade 3 or higher IRRs or; inability to administer the next dose due to a drug-related adverse event or a delay of the administration of the next dose due to toxicities for more than 14 days despite adequate medication or; drug-related grade 4 febrile neutropenia or; drug-related grade 4 anemia which cannot be adequately treated.

  Up to 3.6 years

• Phase 2: Overall Response Rate (ORR)

  ORR is defined as the sum of Complete remission (CR), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) at the ARGX-110 RP2D level that was established in Phase 1 according to established response criteria for Acute myeloid leukemia (AML).

  Up to 3.6 years

Secondary Outcomes (28)

• Phase 1 and Phase 2: Number of Participants with Adverse Events

  Up to 3.6 years

• Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of ARGX-110

  Up to 3.6 years

• Phase 1 and Phase 2: Trough Concentration (Ctrough) of ARGX-110

  Up to 3.6 years

• Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve from Time Zero to Infinite (AUC[0-infinity]) of ARGX-110

  Up to 3.6 years

• Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCtau)

  Up to 3.6 years

Study Arms (1)

ARGX-110 with Azacytidine (AZA)

EXPERIMENTAL

Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m\^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m\^2 BSA, administered SC/IV as per local practice.

Drug: ARGX-110; Drug: AZA

Interventions

ARGX-110 DRUG

ARGX-110 will be administered intravenously.

Also known as: Cusatuzumab, JNJ-74494550

ARGX-110 with Azacytidine (AZA)

AZA DRUG

AZA will be administered subcutaneously/intravenously.

ARGX-110 with Azacytidine (AZA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF) indicating an understanding of the purposes, risks, and procedures required for the study and willingness and ability to participate in the study
• Acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) (according to 2016 World Health Organization \[WHO\] classification definition of greater than or equal to \[\>=\] 20 percent \[%\] blasts) (bone marrow) unsuitable for intensive treatment (including stem cell transplantation) with a curative intent, but eligible to receive azacytidine (AZA) treatment
• Expected life expectancy \>= 3 months, at the discretion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Women of childbearing potential having a negative serum pregnancy test at screening and within 48 hours before infusion of ARGX-110 on Day -14, and willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) during the study and for at least 3 months after the last study drug administration

You may not qualify if:

• Prior or concurrent malignancy, except for the following: (1) adequately treated basal cell or squamous cell skin cancer; (2) carcinoma in situ of the cervix; (3) carcinoma in situ of the breast; (4) incidental histological finding of Prostate cancer (Tumour, Node, Metastasis \[TNM\] stage T1a or T1b), or; (5) Any other cancer from which the subject has been disease-free for more than 2 years
• Any previous AML or MDS chemo- or radiotherapy (with the exception of hydroxyurea/Litalir for leukocyte control which should be discontinued by the first day of AZA, local radiation therapy, therapy for basal or squamous cell carcinoma of the skin)
• Treatment with any investigational product within 4 weeks before the first administration of ARGX-110
• Any known active or chronic infection, including human immunodeficiency virus (HIV) and hepatitis B or C virus infection
• Any other concurrent disease or medical condition that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study

Sponsors & Collaborators

• OncoVerity, Inc.: lead
• argenx: collaborator
• Janssen Research & Development, LLC: collaborator

Study Sites (7)

Unknown Facility

Marseille, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Pierre-Bénite, France

Location

Unknown Facility

Toulouse, France

Location

Unknown Facility

Aarau, Switzerland

Location

Unknown Facility

Bern, Switzerland

Location

Unknown Facility

Zurich, Switzerland

Location

Related Publications (1)

• Riether C, Pabst T, Hopner S, Bacher U, Hinterbrandner M, Banz Y, Muller R, Manz MG, Gharib WH, Francisco D, Bruggmann R, van Rompaey L, Moshir M, Delahaye T, Gandini D, Erzeel E, Hultberg A, Fung S, de Haard H, Leupin N, Ochsenbein AF. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020 Sep;26(9):1459-1467. doi: 10.1038/s41591-020-0910-8. Epub 2020 Jun 29.

  PMID: 32601337 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: January 25, 2017
• Study Start: December 1, 2016
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2022
• Last Updated: August 9, 2023

Record last verified: 2023-08

Locations

FR (4); CH (3)