MCLA-117 in Acute Myelogenous Leukemia

NCT03038230 | Terminated Phase 1 DMC

• 2 other identifiers: MCLA-117-CL012015-003704-23
• Study Type: interventional
• Target: 80
• Locations: 5 countries
• Sites: 9

Brief Summary

This is a First-in-Human, single arm, open-label, multi-national study designed to determine the safety, tolerability and preliminary efficacy of MCLA 117.

Conditions

Acute Myelogenous Leukemia; Acute Myeloid Leukemia

Keywords

human bispecific full length IgG antibody, CLEC12A, CD3; MCLA-117; First in Human; Antibodies, Bispecific; Immunologic Factors; relapsed, refractory patient; AML, minimal residual disease (MRD); Acute Myelogenous Leukemia; Acute Myeloid Leukemia; CD34+CD38; T-cell recruiting

Outcome Measures

Primary Outcomes (1)

• Number of participants with Dose Limiting Toxicities (DLT)

  Evaluation of number of participants with treatment related toxicity observed during a dose escalation step for 1 Cycle

  28 days

Secondary Outcomes (12)

• Maximum plasma concentration [Cmax]

  Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI

• Clearance of plasma

  Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI

• Volume of distribution at steady state [Vss]

  Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI

• Time to reach maximum plasma concentration [Tmax]

  Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI

• Half-life [t1/2]

  Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI

Study Arms (1)

MCLA-117 bispecific antibody

EXPERIMENTAL

Dose escalation cohorts, with escalating doses of MCLA-117 until MTD or RP2D is reached. The dose is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment. Part 2-Expansion Cohort: The RP2D of MCLA-117 is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment.

Drug: MCLA-117 bispecific antibody

Interventions

MCLA-117 bispecific antibody DRUG

MCLA-117, a human bispecific IgG antibody which targets CLEC12A and CD3

Also known as: bispecific, human bispecific common light chain, bispecific IgG1 targeting CLEC12A and CD3

MCLA-117 bispecific antibody

Eligibility Criteria

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

You may qualify if:

• Male or female age ≥18 years old;
• Signed informed consent form
• One of the two following:
• i) AML either de novo or secondary \[any subtype except acute promyelocytic leukemia (APL)\] who either:
• are in relapse to standard therapy following an initial response
• failed primary induction therapy with no CR (failed ≥2 courses of intensive induction therapy. Intensive chemotherapy defined as an intensity of ≥ 5+2)
• newly diagnosed untreated AML in patients ≥ 65 years of age with high risk cytogenetics, if they are not candidates for standard available induction chemotherapy
• AML secondary to MDS, either relapsed or refractory, previously treated with hypomethylating agents for at least 4 cycles;
• Relapsed or refractory AML unfit for intensive chemotherapy previously treated with a low intensity regimen (e.g. low dose Ara-c, hypomethylating agent, etc.) including Venetoclax for at least 2 cycles;
• OR ii) MDS patients who meet the following criteria: very high-risk disease (IPSS-R score \> 6, Greenberg et al., 2012), either relapsed or refractory, previously treated with hypomethylating agents for at least 4 cycles;
• Must have baseline BM sample taken by BMA/BMB within 28 days prior to first dose of MCLA-117 for CLEC12A detection;
• Estimated life expectancy of at least 8 weeks;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
• Significant toxicities incurred as a result of previous anti-cancer therapy resolved to ≤ Grade 1 (NCI-CTCAE version 4.03);
• Acceptable laboratory values at screening;

You may not qualify if:

• Diagnosis of chronic myelogenous leukemia in blast crisis;
• For patients in Cohort B of Part 2, prior hematopoietic stem cell transplantation is allowed under certain circumstances.
• Treatment with anticancer medications, investigational drugs or radiotherapy is allowed within 2 weeks or 5 half-lives prior to start of MCLA-117;
• Previous receipt of live vaccines in the 4 weeks prior to study drug administration;
• Chronic concurrent need of use of corticosteroids \> 10 mg/day of oral prednisone or the equivalent, except topical preparations (e.g., topical creams, steroid inhaler, nasal spray or ophthalmic solution);
• Use of immunosuppressant medications within 4 weeks of MCLA-117 administration;
• Clinically active central nervous system (CNS) leukemia;
• Patients who are pregnant or lactating;
• Patients with an active infection or with an unexplained fever during screening or on the first scheduled day of dosing;
• Patients with known hypersensitivity to any of the components of MCLA-117 or who have had prior hypersensitivity reactions to human or humanized monoclonal antibodies;
• Patients with known HIV, hepatitis B or C;
• Patients with New York Heart Association Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 50%, or significant uncontrolled cardiac disease, current diagnosis of unstable angina, uncontrolled congestive heart failure, new myocardial infarction, or ventricular arrhythmia requiring medication;
• Prior malignancy (other than basal cell carcinoma and cervical in situ carcinoma) unless treated with a curative intend and without evidence of malignant disease for 1 year before screening. Patients with prior hematologic malignancies that have progressed to AML (such as Myelodysplastic syndrome, myeloproliferative neoplasms, bi-phenotypic leukemias, AcuteLymphocyticLeukemia) or AML that has relapsed are eligible;
• Urinary protein \>2+ possibly indicative of renal disease. If the 24 hours urine protein shows a result of \< 100 mg protein, subject can be eligible;
• Patients with any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results;

Sponsors & Collaborators

• Merus B.V.: lead

Study Sites (9)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Ziekenhuis Netwerk Antwerpen Campus Stuivenberg

Antwerp, 2060, Belgium

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

Fondazione Policlinico Tor Vergata

Rome, 00133, Italy

Location

Amsterdam UMC, location VUmc

Amsterdam, North Holland, 1081HV, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, Netherlands

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Neoplasm, Residual

Interventions

CD3 Complex

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Jorge Cortes, MD, PhD

  Independent Protocol Advisor

  PRINCIPAL INVESTIGATOR

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 26, 2017
• First Posted: January 31, 2017
• Study Start: April 1, 2016
• Primary Completion: May 11, 2021
• Study Completion: May 11, 2021
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); BE (1); FR (1); IT (1); NL (3)