MCLA-117 in Acute Myelogenous Leukemia

Inclusion Criteria

• 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;
• Male patients must agree to use an adequate and medically accepted method of contraception throughout the study and for at least 6 months after if their sexual partners are women of child bearing potential (WOCBP).
• WOCBP must be using highly effective and medically accepted method of contraception to avoid pregnancy throughout the study and for at least 6 months after the study ;
• WOCBP must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug.
• Peripheral blast count </= 30,000/mm3 at the time of initiation of infusion on Cycle 1 Day 1.
• Able and willing to comply with all study procedures.

Exclusion Criteria

• Diagnosis of chronic myelogenous leukemia in blast crisis;
• Prior hematopoietic stem cell transplantation (this exclusion applies for dose escalation Part 1 and Cohort A of Part 2);
• 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;
• WOCBP or males with a WOCB partners not willing to use highly effective and medically accepted methods of contraception for 6 months after last study drug administration.
• Need for concurrent other cytoreductive chemotherapy.